Proteomics data analysis: heart

1 Background

Researchers have assessed the proteome in different regions of the heart for 3 patients (identifiers 3, 4, and 8). For each patient they sampled the left atrium (LA), right atrium (RA), left ventricle (LV) and the right ventricle (RV). The data are a small subset of the public dataset PXD006675 on PRIDE.

Suppose that researchers are mainly interested in comparing the ventricular to the atrial proteome. Particularly, they would like to compare the left atrium to the left ventricle, the right atrium to the right ventricle, the average ventricular vs atrial proteome and if ventricular vs atrial proteome shifts differ between left and right heart region.

2 Data

We first import the peptides.txt file. This is the file that contains your peptide-level intensities. For a MaxQuant search [6], this peptides.txt file can be found by default in the “path_to_raw_files/combined/txt/” folder from the MaxQuant output, with “path_to_raw_files” the folder where raw files were saved. In this tutorial, we will use a MaxQuant peptides file from MaxQuant that can be found in the data tree of the SGA2020 github repository https://github.com/statOmics/SGA2020/tree/data/quantification/heart .

To import the data we use the QFeatures package.

We generate the object peptideRawFile with the path to the peptideRaws.txt file. Using the grepEcols function, we find the columns that contain the expression data of the peptideRaws in the peptideRaws.txt file.

library(tidyverse)
library(limma)
library(QFeatures)
library(msqrob2)
library(plotly)

peptidesFile <- "https://raw.githubusercontent.com/statOmics/SGA2020/data/quantification/heart/peptides.txt"

ecols <- MSnbase::grepEcols(
  peptidesFile,
  "Intensity ",
  split = "\t")

pe <- readQFeatures(
  table = peptidesFile,
  fnames = 1,
  ecol = ecols,
  name = "peptideRaw", sep="\t")

pe

## An instance of class QFeatures containing 1 assays:
##  [1] peptideRaw: SummarizedExperiment with 31319 rows and 12 columns

pe[["peptideRaw"]]

## class: SummarizedExperiment 
## dim: 31319 12 
## metadata(0):
## assays(1): ''
## rownames(31319): AAAAAAAAAK AAAAAAAAEQQSSNGPVK ... YYTPVPCESATAK
##   YYTYLIMNK
## rowData names(91): Sequence N.term.cleavage.window ...
##   Oxidation..M..site.IDs MS.MS.Count
## colnames(12): Intensity.LA3 Intensity.LA4 ... Intensity.RV4
##   Intensity.RV8
## colData names(0):

We will make use from data wrangling functionalities from the tidyverse package. The %>% operator allows us to pipe the output of one function to the next function.

colData(pe)$location <- substr(
  colnames(pe[["peptideRaw"]]),
  11,
  11) %>%
  unlist %>%
  as.factor

colData(pe)$tissue <- substr(
    colnames(pe[["peptideRaw"]]),
    12,
    12) %>%
    unlist %>%
    as.factor

colData(pe)$patient <- substr(
  colnames(pe[["peptideRaw"]]),
  13,
  13) %>%
  unlist %>%
  as.factor

We calculate how many non zero intensities we have per peptide and this will be useful for filtering.

rowData(pe[["peptideRaw"]])$nNonZero <- rowSums(assay(pe[["peptideRaw"]]) > 0)

Peptides with zero intensities are missing peptides and should be represent with a NA value rather than 0.

pe <- zeroIsNA(pe, "peptideRaw") # convert 0 to NA

2.1 Data exploration

We can inspect the missingness in our data with the plotNA() function provided with MSnbase. 63% of all peptide intensities are missing and for some peptides we do not even measure a signal in any sample. The missingness is similar across samples.

MSnbase::plotNA(assay(pe[["peptideRaw"]])) +
  xlab("Peptide index (ordered by data completeness)")

3 Preprocessing

This section preforms standard preprocessing for the peptide data. This include log transformation, filtering and summarisation of the data.

3.1 Log transform the data

pe <- logTransform(pe, base = 2, i = "peptideRaw", name = "peptideLog")
limma::plotDensities(assay(pe[["peptideLog"]]))

3.2 Filtering

3.2.1 Handling overlapping protein groups

In our approach a peptide can map to multiple proteins, as long as there is none of these proteins present in a smaller subgroup.

pe <- filterFeatures(pe,
  ~ Proteins %in% smallestUniqueGroups(rowData(pe[["peptideLog"]])$Proteins)
)

3.2.2 Remove reverse sequences (decoys) and contaminants

We now remove the contaminants, peptides that map to decoy sequences, and proteins which were only identified by peptides with modifications.

First look to the names of the variables for the peptide features

pe[["peptideLog"]] %>%
  rowData %>%
  names

##  [1] "Sequence"                "N.term.cleavage.window" 
##  [3] "C.term.cleavage.window"  "Amino.acid.before"      
##  [5] "First.amino.acid"        "Second.amino.acid"      
##  [7] "Second.last.amino.acid"  "Last.amino.acid"        
##  [9] "Amino.acid.after"        "A.Count"                
## [11] "R.Count"                 "N.Count"                
## [13] "D.Count"                 "C.Count"                
## [15] "Q.Count"                 "E.Count"                
## [17] "G.Count"                 "H.Count"                
## [19] "I.Count"                 "L.Count"                
## [21] "K.Count"                 "M.Count"                
## [23] "F.Count"                 "P.Count"                
## [25] "S.Count"                 "T.Count"                
## [27] "W.Count"                 "Y.Count"                
## [29] "V.Count"                 "U.Count"                
## [31] "O.Count"                 "Length"                 
## [33] "Missed.cleavages"        "Mass"                   
## [35] "Proteins"                "Leading.razor.protein"  
## [37] "Start.position"          "End.position"           
## [39] "Gene.names"              "Protein.names"          
## [41] "Unique..Groups."         "Unique..Proteins."      
## [43] "Charges"                 "PEP"                    
## [45] "Score"                   "Identification.type.LA3"
## [47] "Identification.type.LA4" "Identification.type.LA8"
## [49] "Identification.type.LV3" "Identification.type.LV4"
## [51] "Identification.type.LV8" "Identification.type.RA3"
## [53] "Identification.type.RA4" "Identification.type.RA8"
## [55] "Identification.type.RV3" "Identification.type.RV4"
## [57] "Identification.type.RV8" "Fraction.Average"       
## [59] "Fraction.Std..Dev."      "Fraction.1"             
## [61] "Fraction.2"              "Fraction.3"             
## [63] "Fraction.4"              "Fraction.5"             
## [65] "Fraction.6"              "Fraction.7"             
## [67] "Fraction.8"              "Fraction.100"           
## [69] "Experiment.LA3"          "Experiment.LA4"         
## [71] "Experiment.LA8"          "Experiment.LV3"         
## [73] "Experiment.LV4"          "Experiment.LV8"         
## [75] "Experiment.RA3"          "Experiment.RA4"         
## [77] "Experiment.RA8"          "Experiment.RV3"         
## [79] "Experiment.RV4"          "Experiment.RV8"         
## [81] "Intensity"               "Reverse"                
## [83] "Potential.contaminant"   "id"                     
## [85] "Protein.group.IDs"       "Mod..peptide.IDs"       
## [87] "Evidence.IDs"            "MS.MS.IDs"              
## [89] "Best.MS.MS"              "Oxidation..M..site.IDs" 
## [91] "MS.MS.Count"             "nNonZero"

No information on decoys.

pe <- filterFeatures(pe, ~ Potential.contaminant != "+")

3.2.3 Remove peptides of proteins that were only identified with modified peptides

I will skip this step for the moment. Large protein groups file needed for this.

3.2.4 Drop peptides that were only identified in one sample

We keep peptides that were observed at last twice.

pe <- filterFeatures(pe, ~ nNonZero >= 2)
nrow(pe[["peptideLog"]])

## [1] 17432

We keep 17432 peptides after filtering.

3.3 Quantile normalize the data

pe <- normalize(pe, i = "peptideLog", method = "quantiles", name = "peptideNorm")

3.4 Explore quantile normalized data

After quantile normalisation the density curves for all samples coincide.

limma::plotDensities(assay(pe[["peptideNorm"]]))

This is more clearly seen is a boxplot.

boxplot(assay(pe[["peptideNorm"]]), col = palette()[-1],
       main = "Peptide distribtutions after normalisation", ylab = "intensity")

We can visualize our data using a Multi Dimensional Scaling plot, eg. as provided by the limma package.

limma::plotMDS(assay(pe[["peptideNorm"]]),
  col = colData(pe)$location:colData(pe)$tissue %>%
    as.numeric,
  labels = colData(pe) %>%
    rownames %>%
    substr(start = 11, stop = 13)
  )

The first axis in the plot is showing the leading log fold changes (differences on the log scale) between the samples.

3.5 Summarization to protein level

We use robust summarization in aggregateFeatures. This is the default workflow of aggregateFeatures so you do not have to specifiy the argument fun. However, because we compare methods we have included the fun argument to show the summarization method explicitely.

pe <- aggregateFeatures(pe,
 i = "peptideNorm",
 fcol = "Proteins",
 na.rm = TRUE,
 name = "proteinRobust",
 fun = MsCoreUtils::robustSummary)

## Your quantitative and row data contain missing values. Please read the
## relevant section(s) in the aggregateFeatures manual page regarding the
## effects of missing values on data aggregation.

plotMDS(assay(pe[["proteinRobust"]]),
  col = colData(pe)$location:colData(pe)$tissue %>%
    as.numeric,
  labels = colData(pe) %>%
    rownames %>%
    substr(start = 11, stop = 13)
)

4 Data Analysis

4.1 Estimation

We model the protein level expression values using msqrob. By default msqrob2 estimates the model parameters using robust regression.

pe <- msqrob(
  object = pe,
  i = "proteinRobust",
  formula = ~ location*tissue + patient)

4.2 Inference

First, we extract the parameter names of the model.

getCoef(rowData(pe[["proteinRobust"]])$msqrobModels[[2]])

##       (Intercept)         locationR           tissueV          patient4 
##       26.33779939        0.28826213        0.20946392        0.46536955 
##          patient8 locationR:tissueV 
##       -0.02608046       -0.05550111

L <- makeContrast(
  c(
    "tissueV = 0",
    "tissueV + locationR:tissueV = 0",
    "tissueV + 0.5*locationR:tissueV = 0","locationR:tissueV = 0"),
  parameterNames =
    rowData(pe[["proteinRobust"]])$msqrobModels[[2]] %>%
    getCoef %>%
    names
  )


pe <- hypothesisTest(object = pe, i = "proteinRobust", contrast = L, overwrite=TRUE)

4.3 Evaluate results contrast \(\log_2 FC_{V-A}^L\)

4.3.1 Volcano-plot

volcanoLeft <- ggplot(rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV",
                 aes(x = logFC, y = -log10(pval), color = adjPval < 0.05)) +
 geom_point(cex = 2.5) +
 scale_color_manual(values = alpha(c("black", "red"), 0.5)) + theme_minimal()
volcanoLeft

4.3.2 Heatmap

We first select the names of the proteins that were declared signficant.

sigNamesLeft <- rowData(pe[["proteinRobust"]])$tissueV %>%
 rownames_to_column("proteinRobust") %>%
 filter(adjPval<0.05) %>%
 pull(proteinRobust)
heatmap(assay(pe[["proteinRobust"]])[sigNamesLeft, ])

There are 211 proteins significantly differentially expressed at the 5% FDR level.

rowData(pe[["proteinRobust"]])$tissueV %>%
  cbind(.,rowData(pe[["proteinRobust"]])$Protein.names) %>%
  na.exclude %>%
  filter(adjPval<0.05) %>%
  arrange(pval)  %>%
  knitr::kable(.)

	logFC	se	df	t	pval	adjPval	rowData(pe[[“proteinRobust”]])$Protein.names
P08590	7.566945	0.4227679	9.117912	17.898582	0.0000000	0.0000417	Myosin light chain 3
P12883	4.333125	0.3637861	9.255194	11.911187	0.0000006	0.0006480	Myosin-7
P10916	6.908674	0.5190748	7.385413	13.309594	0.0000020	0.0013463	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
O75368	-2.290376	0.2718512	9.251939	-8.425109	0.0000123	0.0046575	SH3 domain-binding glutamic acid-rich-like protein
P46821	-2.182822	0.2654404	9.385413	-8.223396	0.0000137	0.0046575	Microtubule-associated protein 1B;MAP1B heavy chain;MAP1 light chain LC1
Q6UWY5	-3.253229	0.3888996	9.170135	-8.365215	0.0000138	0.0046575	Olfactomedin-like protein 1
Q8N474	-3.304647	0.3784419	7.847514	-8.732243	0.0000261	0.0070102	Secreted frizzled-related protein 1
O95865	-2.158932	0.2871753	9.385413	-7.517818	0.0000288	0.0070102	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
Q9ULL5-3	-3.386308	0.3993822	7.893242	-8.478865	0.0000311	0.0070102	Proline-rich protein 12
P02452	-3.226193	0.4112622	8.367424	-7.844614	0.0000392	0.0070838	Collagen alpha-1(I) chain
O94875-10	2.321238	0.3122508	8.958355	7.433891	0.0000406	0.0070838	Sorbin and SH3 domain-containing protein 2
Q16647	-2.787698	0.3824272	9.156725	-7.289485	0.0000422	0.0070838	Prostacyclin synthase
P29622	-2.114870	0.2991501	9.385413	-7.069595	0.0000474	0.0070838	Kallistatin
P14854	2.300663	0.3037112	8.346841	7.575168	0.0000514	0.0070838	Cytochrome c oxidase subunit 6B1
P05546	-1.915671	0.2708975	9.198639	-7.071573	0.0000523	0.0070838	Heparin cofactor 2
P21810	-3.380254	0.4548500	8.304055	-7.431580	0.0000609	0.0077217	Biglycan
P36955	-2.323620	0.3325722	8.456893	-6.986813	0.0000872	0.0097521	Pigment epithelium-derived factor
P23083	-4.274293	0.5581240	7.385413	-7.658322	0.0000912	0.0097521	Ig heavy chain V-I region V35
P13533	-4.313925	0.6516590	9.115028	-6.619911	0.0000915	0.0097521	Myosin-6
Q15113	-2.755021	0.4253583	9.188121	-6.476942	0.0001043	0.0097521	Procollagen C-endopeptidase enhancer 1
Q9UBG0	-2.576210	0.3963719	9.131671	-6.499476	0.0001044	0.0097521	C-type mannose receptor 2
P00325	-2.108814	0.3251595	9.141096	-6.485476	0.0001057	0.0097521	Alcohol dehydrogenase 1B
P07451	-1.841539	0.2910138	9.385413	-6.328012	0.0001136	0.0100264	Carbonic anhydrase 3
P51888	-3.199549	0.4165978	6.959924	-7.680186	0.0001217	0.0102934	Prolargin
P24844	-2.551801	0.4140400	9.330669	-6.163176	0.0001427	0.0112127	Myosin regulatory light polypeptide 9
Q53GQ0	-2.430853	0.3948274	9.334954	-6.156748	0.0001436	0.0112127	Very-long-chain 3-oxoacyl-CoA reductase
Q06828	-4.209189	0.6775919	9.003303	-6.211983	0.0001564	0.0116347	Fibromodulin
Q8TBQ9	-2.761806	0.4223033	8.170120	-6.539863	0.0001643	0.0116347	Protein kish-A
P51884	-2.402234	0.3614104	7.936878	-6.646831	0.0001672	0.0116347	Lumican
P35442	-2.334260	0.3655617	8.385413	-6.385405	0.0001735	0.0116347	Thrombospondin-2
Q9UL18	-2.602312	0.3982234	8.037138	-6.534804	0.0001777	0.0116347	Protein argonaute-1
Q96LL9	-2.426640	0.3958291	8.842792	-6.130526	0.0001858	0.0117873	DnaJ homolog subfamily C member 30
P18428	-2.002578	0.3365444	9.013977	-5.950411	0.0002139	0.0131587	Lipopolysaccharide-binding protein
P08294	-2.756458	0.4335622	7.979491	-6.357699	0.0002212	0.0132069	Extracellular superoxide dismutase [Cu-Zn]
P36021	-3.138301	0.5174695	8.385413	-6.064707	0.0002493	0.0136858	Monocarboxylate transporter 8
P02743	-2.273778	0.3999916	9.385413	-5.684565	0.0002568	0.0136858	Serum amyloid P-component;Serum amyloid P-component(1-203)
Q8WWA0	-5.806975	0.9532620	8.244689	-6.091688	0.0002588	0.0136858	Intelectin-1
Q92736-2	-3.330740	0.5744993	8.908498	-5.797640	0.0002706	0.0136858	Ryanodine receptor 2
O60760	-3.500029	0.5842390	8.385413	-5.990748	0.0002715	0.0136858	Hematopoietic prostaglandin D synthase
Q9UGT4	-2.283615	0.4020386	9.193722	-5.680088	0.0002789	0.0136858	Sushi domain-containing protein 2
Q14764	-1.625976	0.2901417	9.385413	-5.604074	0.0002855	0.0136858	Major vault protein
O95980	-2.552421	0.4176977	7.980660	-6.110688	0.0002889	0.0136858	Reversion-inducing cysteine-rich protein with Kazal motifs
Q92508	4.071001	0.5712249	6.385413	7.126791	0.0002899	0.0136858	Piezo-type mechanosensitive ion channel component 1
Q9BW30	-2.738684	0.4828316	9.049210	-5.672131	0.0002988	0.0137863	Tubulin polymerization-promoting protein family member 3
P12110	-2.136456	0.3667316	8.535409	-5.825667	0.0003078	0.0138861	Collagen alpha-2(VI) chain
P40261	-2.306727	0.4169709	9.340024	-5.532105	0.0003196	0.0141028	Nicotinamide N-methyltransferase
P05997	-3.068864	0.5429778	8.864434	-5.651913	0.0003308	0.0141028	Collagen alpha-2(V) chain
Q9P2B2	-2.047509	0.3731311	9.385413	-5.487374	0.0003335	0.0141028	Prostaglandin F2 receptor negative regulator
Q9NZ01	-2.346040	0.4161143	8.691035	-5.637970	0.0003618	0.0148853	Very-long-chain enoyl-CoA reductase
P46060	-1.970642	0.3436046	8.385413	-5.735204	0.0003666	0.0148853	Ran GTPase-activating protein 1
P31994-2	-1.655566	0.3017732	8.992524	-5.486128	0.0003882	0.0152351	Low affinity immunoglobulin gamma Fc region receptor II-b
O14967	-2.393131	0.4223134	8.430438	-5.666718	0.0003903	0.0152351	Calmegin
P00748	-2.003056	0.3702529	9.091376	-5.409968	0.0004128	0.0156430	Coagulation factor XII;Coagulation factor XIIa heavy chain;Beta-factor XIIa part 1;Coagulation factor XIIa light chain
Q07954	-1.674832	0.3146216	9.385413	-5.323322	0.0004161	0.0156430	Prolow-density lipoprotein receptor-related protein 1;Low-density lipoprotein receptor-related protein 1 85 kDa subunit;Low-density lipoprotein receptor-related protein 1 515 kDa subunit;Low-density lipoprotein receptor-related protein 1 intracellular domain
Q9UBB5	2.673301	0.4015137	6.385413	6.658059	0.0004277	0.0157858	Methyl-CpG-binding domain protein 2
O43677	-2.758090	0.4792076	7.933870	-5.755523	0.0004396	0.0159350	NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
Q92604	-2.270281	0.4316583	9.345516	-5.259442	0.0004605	0.0163992	Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
Q8NAT1	-1.416451	0.2751694	9.385413	-5.147559	0.0005298	0.0181178	Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2
O00264	-1.999242	0.3827164	9.079390	-5.223821	0.0005311	0.0181178	Membrane-associated progesterone receptor component 1
Q92621	-1.755581	0.3415656	9.385413	-5.139808	0.0005355	0.0181178	Nuclear pore complex protein Nup205
Q8WZA9	-1.502201	0.2907398	9.101344	-5.166822	0.0005690	0.0186760	Immunity-related GTPase family Q protein
Q9BXN1	-2.670923	0.5132981	8.937487	-5.203455	0.0005742	0.0186760	Asporin
Q14195-2	-2.527278	0.4943182	9.262403	-5.112654	0.0005796	0.0186760	Dihydropyrimidinase-related protein 3
O00180	-4.096722	0.7724957	8.385413	-5.303229	0.0006215	0.0197142	Potassium channel subfamily K member 1
Q8TBP6	-1.893243	0.3673308	8.851865	-5.154053	0.0006323	0.0197464	Solute carrier family 25 member 40
Q9GZY4	-3.167768	0.5759744	7.703311	-5.499842	0.0006539	0.0198708	Cytochrome c oxidase assembly factor 1 homolog
P41240	-1.569148	0.3075870	8.922337	-5.101476	0.0006615	0.0198708	Tyrosine-protein kinase CSK
Q9NY15	-2.177423	0.4377625	9.336638	-4.973981	0.0006860	0.0198708	Stabilin-1
Q96C86	-1.515572	0.3020943	9.145534	-5.016883	0.0006878	0.0198708	m7GpppX diphosphatase
P02747	-2.680914	0.4712559	7.138784	-5.688871	0.0006937	0.0198708	Complement C1q subcomponent subunit C
P06858	1.795244	0.3596173	9.218266	4.992094	0.0006950	0.0198708	Lipoprotein lipase
O43464	-1.900721	0.3799226	9.072346	-5.002915	0.0007184	0.0201585	Serine protease HTRA2, mitochondrial
O14980	-1.230352	0.2498369	9.382448	-4.924620	0.0007249	0.0201585	Exportin-1
Q8WY22	-1.839442	0.3608464	8.385413	-5.097577	0.0008064	0.0221211	BRI3-binding protein
P04083	-1.524538	0.3158141	9.385413	-4.827329	0.0008320	0.0225191	Annexin A1
P48681	-1.330081	0.2756444	9.321612	-4.825351	0.0008507	0.0227223	Nestin
P02775	-1.952126	0.4075050	9.385413	-4.790435	0.0008772	0.0229385	Platelet basic protein;Connective tissue-activating peptide III;TC-2;Connective tissue-activating peptide III(1-81);Beta-thromboglobulin;Neutrophil-activating peptide 2(74);Neutrophil-activating peptide 2(73);Neutrophil-activating peptide 2;TC-1;Neutrophil-activating peptide 2(1-66);Neutrophil-activating peptide 2(1-63)
Q7L4S7	-1.747450	0.3202677	7.157555	-5.456217	0.0008814	0.0229385	Protein ARMCX6
P46063	-1.386912	0.2873890	9.154885	-4.825907	0.0008948	0.0229922	ATP-dependent DNA helicase Q1
A6NMZ7	-2.267329	0.4773591	9.385413	-4.749734	0.0009302	0.0232949	Collagen alpha-6(VI) chain
Q5NDL2	-2.337629	0.4766026	8.686198	-4.904777	0.0009340	0.0232949	EGF domain-specific O-linked N-acetylglucosamine transferase
P56539	-2.051918	0.4159611	8.553679	-4.932956	0.0009410	0.0232949	Caveolin-3
Q9UNW9	4.097053	0.8545595	9.054127	4.794344	0.0009650	0.0236026	RNA-binding protein Nova-2
P01699	-4.025961	0.6965009	6.314916	-5.780266	0.0009792	0.0236632	Ig lambda chain V-I region VOR
Q9HAV4	-2.205274	0.4388018	7.987893	-5.025671	0.0010243	0.0244630	Exportin-5
Q92681	-2.153054	0.4353071	8.133279	-4.946057	0.0010730	0.0253280	Regulatory solute carrier protein family 1 member 1
P49207	-1.534829	0.3249990	8.970773	-4.722565	0.0010949	0.0255013	60S ribosomal protein L34
P50552	-1.523119	0.3245142	9.074476	-4.693535	0.0011055	0.0255013	Vasodilator-stimulated phosphoprotein
Q5VIR6-4	-1.755057	0.3758054	9.130015	-4.670123	0.0011243	0.0256432	Vacuolar protein sorting-associated protein 53 homolog
Q96H79	-3.021670	0.5420367	6.334231	-5.574659	0.0011785	0.0265817	Zinc finger CCCH-type antiviral protein 1-like
O75828	-1.641739	0.3592450	9.385413	-4.569971	0.0012087	0.0269634	Carbonyl reductase [NADPH] 3
O15230	-1.415011	0.3058820	9.044210	-4.626004	0.0012277	0.0270900	Laminin subunit alpha-5
Q5M9N0	-3.537066	0.7427497	8.350040	-4.762123	0.0012639	0.0275884	Coiled-coil domain-containing protein 158
P04196	-1.917181	0.3881943	7.683140	-4.938714	0.0012797	0.0276358	Histidine-rich glycoprotein
Q53GG5-2	-2.923374	0.6214767	8.429675	-4.703916	0.0013308	0.0282214	PDZ and LIM domain protein 3
Q6SZW1	-2.563687	0.5126523	7.385413	-5.000831	0.0013346	0.0282214	Sterile alpha and TIR motif-containing protein 1
Q15274	-1.928288	0.3958755	7.757883	-4.870945	0.0013525	0.0283041	Nicotinate-nucleotide pyrophosphorylase [carboxylating]
Q9BXR6	-2.352662	0.5252419	9.382448	-4.479196	0.0013831	0.0283325	Complement factor H-related protein 5
Q9ULC3	-1.674808	0.3626400	8.669265	-4.618376	0.0013874	0.0283325	Ras-related protein Rab-23
Q9Y5U8	-3.988833	0.8897580	9.327097	-4.483053	0.0013957	0.0283325	Mitochondrial pyruvate carrier 1
P34932	-1.163429	0.2608932	9.385413	-4.459407	0.0014232	0.0286058	Heat shock 70 kDa protein 4
Q9BUF5	-1.934378	0.4345654	9.217423	-4.451293	0.0015060	0.0298342	Tubulin beta-6 chain
Q8TDB6	-1.611315	0.3613218	9.153547	-4.459500	0.0015138	0.0298342	E3 ubiquitin-protein ligase DTX3L
P45877	-1.259792	0.2861984	9.343571	-4.401814	0.0015676	0.0305974	Peptidyl-prolyl cis-trans isomerase C
P04003	-1.479053	0.3338506	9.090898	-4.430283	0.0016066	0.0310601	C4b-binding protein alpha chain
P06727	-1.358368	0.3048521	8.884167	-4.455826	0.0016384	0.0312643	Apolipoprotein A-IV
P09619	-1.675728	0.3807310	9.154490	-4.401345	0.0016479	0.0312643	Platelet-derived growth factor receptor beta
Q8N5M1	-2.022143	0.4573254	8.937206	-4.421672	0.0016958	0.0316965	ATP synthase mitochondrial F1 complex assembly factor 2
Q6YN16	1.527167	0.3496754	9.222955	4.367385	0.0017019	0.0316965	Hydroxysteroid dehydrogenase-like protein 2
P01042	-2.256316	0.4659486	7.210294	-4.842414	0.0017231	0.0317986	Kininogen-1;Kininogen-1 heavy chain;T-kinin;Bradykinin;Lysyl-bradykinin;Kininogen-1 light chain;Low molecular weight growth-promoting factor
P08582	-1.663860	0.3857501	9.299314	-4.313310	0.0018093	0.0329078	Melanotransferrin
P30405	-1.540274	0.3587630	9.385413	-4.293290	0.0018252	0.0329078	Peptidyl-prolyl cis-trans isomerase F, mitochondrial
P14550	-1.394080	0.3100035	8.301450	-4.496981	0.0018318	0.0329078	Alcohol dehydrogenase [NADP(+)]
Q9UQ35	-1.367511	0.3203946	9.385413	-4.268208	0.0018958	0.0334035	Serine/arginine repetitive matrix protein 2
P36551	-1.338543	0.3106105	9.112223	-4.309393	0.0019078	0.0334035	Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial
P14555	-4.594903	0.9455710	6.867951	-4.859396	0.0019377	0.0334035	Phospholipase A2, membrane associated
Q08945	-2.071352	0.4670698	8.385413	-4.434781	0.0019453	0.0334035	FACT complex subunit SSRP1
P24311	1.725765	0.4048607	9.295713	4.262615	0.0019540	0.0334035	Cytochrome c oxidase subunit 7B, mitochondrial
P02461	-3.597666	0.8096938	8.323445	-4.443242	0.0019581	0.0334035	Collagen alpha-1(III) chain
Q9H1E5	-1.388829	0.3280259	9.385413	-4.233902	0.0019969	0.0337811	Thioredoxin-related transmembrane protein 4
O00303	-1.477605	0.3444231	9.008150	-4.290088	0.0020156	0.0338155	Eukaryotic translation initiation factor 3 subunit F
Q9Y6X5	-1.411435	0.3280595	8.750753	-4.302375	0.0021171	0.0348421	Bis(5-adenosyl)-triphosphatase ENPP4
P15924	1.274221	0.3034579	9.350459	4.199004	0.0021231	0.0348421	Desmoplakin
O75746	-1.578482	0.3695373	8.893946	-4.271509	0.0021327	0.0348421	Calcium-binding mitochondrial carrier protein Aralar1
P05455	-1.204229	0.2854061	9.178555	-4.219353	0.0021455	0.0348421	Lupus La protein
Q2TAA5	-1.319245	0.3143146	9.249693	-4.197212	0.0021804	0.0349673	GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
P04004	-1.633973	0.3854552	8.981078	-4.239073	0.0021876	0.0349673	Vitronectin;Vitronectin V65 subunit;Vitronectin V10 subunit;Somatomedin-B
P01031	-1.322378	0.3017394	8.183937	-4.382518	0.0022165	0.0351530	Complement C5;Complement C5 beta chain;Complement C5 alpha chain;C5a anaphylatoxin;Complement C5 alpha chain
Q5JPH6	3.506017	0.7033283	6.212234	4.984894	0.0022530	0.0354450	Probable glutamate–tRNA ligase, mitochondrial
P49458	-2.320823	0.5006356	7.120983	-4.635753	0.0022768	0.0354450	Signal recognition particle 9 kDa protein
P04209	1.316898	0.3151619	9.167154	4.178483	0.0022873	0.0354450	Ig lambda chain V-II region NIG-84
Q04721	1.531039	0.3675191	9.201253	4.165877	0.0023123	0.0355608	Neurogenic locus notch homolog protein 2;Notch 2 extracellular truncation;Notch 2 intracellular domain
Q9UKS6	1.443688	0.3439564	8.943424	4.197299	0.0023485	0.0358449	Protein kinase C and casein kinase substrate in neurons protein 3
Q9BTV4	-1.810463	0.4381260	9.284468	-4.132288	0.0023862	0.0361484	Transmembrane protein 43
O75348	-1.846417	0.4493725	9.377764	-4.108879	0.0024210	0.0364041	V-type proton ATPase subunit G 1
Q12996	-1.667403	0.3663886	7.207709	-4.550913	0.0024442	0.0364833	Cleavage stimulation factor subunit 3
P60468	-1.522924	0.3550773	8.241407	-4.288994	0.0024787	0.0367280	Protein transport protein Sec61 subunit beta
Q6ZSY5	-1.520789	0.3699133	9.170791	-4.111204	0.0025292	0.0370388	Protein phosphatase 1 regulatory subunit 3F
P62760	-1.929645	0.4686939	9.120970	-4.117068	0.0025362	0.0370388	Visinin-like protein 1
Q14019	-3.973669	0.8363384	6.385413	-4.751270	0.0026690	0.0387005	Coactosin-like protein
Q13478	-1.620268	0.3970937	8.994941	-4.080316	0.0027600	0.0397356	Interleukin-18 receptor 1
P01034	-1.689330	0.4126063	8.837162	-4.094289	0.0028058	0.0401104	Cystatin-C
Q53T59	-1.852124	0.4344248	7.876061	-4.263395	0.0028487	0.0402275	HCLS1-binding protein 3
P02776	-1.748717	0.4069507	7.718405	-4.297123	0.0028536	0.0402275	Platelet factor 4;Platelet factor 4, short form
P26447	-1.877769	0.4593883	8.774968	-4.087542	0.0028764	0.0402690	Protein S100-A4
Q9Y2Z0	-1.757978	0.4412870	9.385413	-3.983751	0.0029317	0.0405660	Suppressor of G2 allele of SKP1 homolog
O75475	-1.951060	0.4885410	9.296501	-3.993647	0.0029426	0.0405660	PC4 and SFRS1-interacting protein
Q1KMD3	-1.494563	0.3712572	9.051770	-4.025682	0.0029575	0.0405660	Heterogeneous nuclear ribonucleoprotein U-like protein 2
P01024	-1.148297	0.2873908	9.197920	-3.995596	0.0029972	0.0408343	Complement C3;Complement C3 beta chain;C3-beta-c;Complement C3 alpha chain;C3a anaphylatoxin;Acylation stimulating protein;Complement C3b alpha chain;Complement C3c alpha chain fragment 1;Complement C3dg fragment;Complement C3g fragment;Complement C3d fragment;Complement C3f fragment;Complement C3c alpha chain fragment 2
P54577	-1.309794	0.3255176	8.964139	-4.023729	0.0030257	0.0409480	Tyrosine–tRNA ligase, cytoplasmic;Tyrosine–tRNA ligase, cytoplasmic, N-terminally processed
P54652	-1.585922	0.3969039	9.007166	-3.995732	0.0031255	0.0420185	Heat shock-related 70 kDa protein 2
P25311	-1.476798	0.3658030	8.673237	-4.037141	0.0031737	0.0422552	Zinc-alpha-2-glycoprotein
Q9UK22	-1.968951	0.4285590	6.372396	-4.594351	0.0031847	0.0422552	F-box only protein 2
O94919	-1.158582	0.2941090	9.248102	-3.939294	0.0032331	0.0425105	Endonuclease domain-containing 1 protein
P03950	-2.214295	0.5408135	8.216113	-4.094379	0.0032737	0.0425105	Angiogenin
O15111	-1.770061	0.4097076	7.141811	-4.320302	0.0033195	0.0425105	Inhibitor of nuclear factor kappa-B kinase subunit alpha
P07357	-1.154912	0.2950375	9.290174	-3.914458	0.0033303	0.0425105	Complement component C8 alpha chain
O15116	-3.262825	0.6533382	5.390877	-4.994083	0.0033442	0.0425105	U6 snRNA-associated Sm-like protein LSm1
Q13641	-2.094962	0.4829370	7.050947	-4.337963	0.0033469	0.0425105	Trophoblast glycoprotein
Q9BS26	-1.226358	0.3132596	9.249914	-3.914830	0.0033564	0.0425105	Endoplasmic reticulum resident protein 44
Q14011	-2.439155	0.5991974	8.231467	-4.070703	0.0033715	0.0425105	Cold-inducible RNA-binding protein
P12814	-1.726195	0.4239901	8.144626	-4.071308	0.0034446	0.0431638	Alpha-actinin-1
P25940	-1.680300	0.4292504	9.043783	-3.914499	0.0035074	0.0436810	Collagen alpha-3(V) chain
Q9UBI9	-2.822134	0.6797511	7.613412	-4.151717	0.0035670	0.0441523	Headcase protein homolog
Q96PK6	-1.284104	0.3320346	9.148490	-3.867380	0.0036883	0.0448514	RNA-binding protein 14
Q7LBR1	-2.851457	0.7432377	9.385413	-3.836534	0.0036895	0.0448514	Charged multivesicular body protein 1b
P07384	-1.106938	0.2881747	9.333139	-3.841205	0.0037006	0.0448514	Calpain-1 catalytic subunit
O60262	-1.514780	0.3809638	8.388576	-3.976177	0.0037118	0.0448514	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
Q86VU5	1.574090	0.4112246	9.385413	3.827810	0.0037405	0.0449299	Catechol O-methyltransferase domain-containing protein 1
Q13636	-3.085924	0.6708563	5.941397	-4.599978	0.0037856	0.0452041	Ras-related protein Rab-31
O43143	-1.010978	0.2650086	9.289616	-3.814887	0.0038896	0.0458869	Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX15
P20774	-2.236773	0.5631895	8.210882	-3.971618	0.0039003	0.0458869	Mimecan
P08311	-1.326822	0.3393339	8.579011	-3.910077	0.0039106	0.0458869	Cathepsin G
A8MTT3	-3.368826	0.8032193	7.070471	-4.194155	0.0039754	0.0461448	Protein CEBPZOS
Q9HB40	-2.173414	0.4870876	6.179009	-4.462060	0.0039780	0.0461448	Retinoid-inducible serine carboxypeptidase
O60476	-2.858033	0.6987082	7.449546	-4.090453	0.0040536	0.0462919	Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB
Q96CS3	-1.329185	0.3488970	9.119924	-3.809678	0.0040557	0.0462919	FAS-associated factor 2
Q04941	-1.954543	0.5132443	9.127049	-3.808212	0.0040591	0.0462919	Proteolipid protein 2
Q8NFQ8	-1.244891	0.3112852	7.843418	-3.999198	0.0041168	0.0466119	Torsin-1A-interacting protein 2
Q9Y3B4	-1.254563	0.3315970	9.218746	-3.783396	0.0041429	0.0466119	Splicing factor 3B subunit 6
O00567	-2.329642	0.6192522	9.376799	-3.762024	0.0041560	0.0466119	Nucleolar protein 56
Q9UKX3	2.040096	0.5408257	9.208912	3.772187	0.0042241	0.0471152	Myosin-13
P56199	-1.282712	0.3337866	8.647866	-3.842911	0.0042549	0.0471986	Integrin alpha-1
P14543	-1.384551	0.3678338	9.204669	-3.764065	0.0042816	0.0472368	Nidogen-1
Q9Y2D4	-1.989829	0.5205860	8.653139	-3.822287	0.0043830	0.0479403	Exocyst complex component 6B
Q6P1N0	-1.699604	0.4098304	6.936107	-4.147091	0.0043979	0.0479403	Coiled-coil and C2 domain-containing protein 1A
Q8NBF2	-1.164826	0.3132700	9.379760	-3.718280	0.0044515	0.0479403	NHL repeat-containing protein 2
P62745	-1.495470	0.3945560	8.788016	-3.790261	0.0044705	0.0479403	Rho-related GTP-binding protein RhoB
Q14254	-1.392125	0.3457572	7.385413	-4.026309	0.0044916	0.0479403	Flotillin-2
Q9Y287	-1.918702	0.5175377	9.385413	-3.707366	0.0045246	0.0479403	Integral membrane protein 2B;BRI2, membrane form;BRI2 intracellular domain;BRI2C, soluble form;Bri23 peptide
P49773	-1.295274	0.3495513	9.385413	-3.705532	0.0045377	0.0479403	Histidine triad nucleotide-binding protein 1
Q9BVC6	-1.637083	0.4433031	9.341936	-3.692921	0.0046665	0.0479403	Transmembrane protein 109
P08670	-1.482725	0.3924566	8.643328	-3.778060	0.0046928	0.0479403	Vimentin
P50991	-1.786149	0.4735903	8.685140	-3.771507	0.0046981	0.0479403	T-complex protein 1 subunit delta
P23434	1.126822	0.3062675	9.385413	3.679208	0.0047316	0.0479403	Glycine cleavage system H protein, mitochondrial
Q6IC98	-1.126652	0.3015080	8.888308	-3.736724	0.0047525	0.0479403	GRAM domain-containing protein 4
Q8IXW5	3.388152	0.8332024	7.009655	4.066422	0.0047569	0.0479403	Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2
Q6P587	5.677610	1.3549193	6.518479	4.190368	0.0047840	0.0479403	Acylpyruvase FAHD1, mitochondrial
P01008	-1.547192	0.4205447	9.310907	-3.679019	0.0047975	0.0479403	Antithrombin-III
P04843	-2.051639	0.5456574	8.660976	-3.759939	0.0048046	0.0479403	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1
Q96FJ2	1.591193	0.4148520	8.139895	3.835568	0.0048186	0.0479403	Dynein light chain 2, cytoplasmic
Q7Z3T8	-1.576843	0.4157303	8.413206	-3.792946	0.0048217	0.0479403	Zinc finger FYVE domain-containing protein 16
P51665	-1.274787	0.3456226	9.194991	-3.688379	0.0048292	0.0479403	26S proteasome non-ATPase regulatory subunit 7
P80723	-1.638540	0.4231920	7.910668	-3.871858	0.0048319	0.0479403	Brain acid soluble protein 1
O95486	-1.500300	0.4068449	9.187800	-3.687646	0.0048413	0.0479403	Protein transport protein Sec24A
Q14258	-1.359986	0.3561261	8.157903	-3.818833	0.0049155	0.0483626	E3 ubiquitin/ISG15 ligase TRIM25
P04275	-1.054100	0.2849243	8.991784	-3.699577	0.0049316	0.0483626	von Willebrand factor;von Willebrand antigen 2
Q16082	-1.361982	0.3713096	9.207589	-3.668050	0.0049745	0.0485490	Heat shock protein beta-2
P32119	-1.348354	0.3464470	7.636769	-3.891950	0.0050302	0.0488581	Peroxiredoxin-2
P05060	-2.649749	0.6720512	7.305570	-3.942778	0.0051268	0.0495588	Secretogranin-1;PE-11;GAWK peptide;CCB peptide
Q9HCB6	-1.808880	0.4871150	8.648303	-3.713455	0.0051666	0.0497073	Spondin-1

4.4 Evaluate results contrast \(\log_2 FC_{V-A}^R\)

4.4.1 Volcano-plot

volcanoRight <- ggplot(rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV",
                 aes(x = logFC, y = -log10(pval), color = adjPval < 0.05)) +
 geom_point(cex = 2.5) +
 scale_color_manual(values = alpha(c("black", "red"), 0.5)) + theme_minimal()
volcanoRight

4.4.2 Heatmap

We first select the names of the proteins that were declared signficant.

sigNamesRight <- rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV" %>%
 rownames_to_column("proteinRobust") %>%
 filter(adjPval<0.05) %>%
 pull(proteinRobust)
heatmap(assay(pe[["proteinRobust"]])[sigNamesRight, ])

There are 94 proteins significantly differentially expressed at the 5% FDR level.

rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV"  %>%
  cbind(.,rowData(pe[["proteinRobust"]])$Protein.names) %>%
  na.exclude %>%
  filter(adjPval<0.05) %>%
  arrange(pval) %>%
  knitr::kable(.)

	logFC	se	df	t	pval	adjPval	rowData(pe[[“proteinRobust”]])$Protein.names
P08590	5.358077	0.4191438	9.117912	12.783387	0.0000004	0.0008046	Myosin light chain 3
P06858	3.329246	0.3542730	9.218266	9.397404	0.0000051	0.0051277	Lipoprotein lipase
P02776	-2.841711	0.3443690	7.718405	-8.251937	0.0000430	0.0194907	Platelet factor 4;Platelet factor 4, short form
P35442	-3.207091	0.4221143	8.385413	-7.597683	0.0000491	0.0194907	Thrombospondin-2
O75368	-1.844075	0.2686680	9.251939	-6.863771	0.0000643	0.0194907	SH3 domain-binding glutamic acid-rich-like protein
P54652	-2.725246	0.4112417	9.007166	-6.626871	0.0000959	0.0194907	Heat shock-related 70 kDa protein 2
Q9ULD0	-3.507028	0.3938799	6.128068	-8.903799	0.0000993	0.0194907	2-oxoglutarate dehydrogenase-like, mitochondrial
A6NMZ7	-3.065958	0.4773591	9.385413	-6.422751	0.0001012	0.0194907	Collagen alpha-6(VI) chain
Q6UWY5	-2.469667	0.3813094	9.170135	-6.476806	0.0001053	0.0194907	Olfactomedin-like protein 1
P21810	-2.994207	0.4377152	8.304055	-6.840536	0.0001110	0.0194907	Biglycan
P05546	-1.750184	0.2755089	9.198639	-6.352548	0.0001204	0.0194907	Heparin cofactor 2
P13533	-4.083951	0.6439331	9.115028	-6.342197	0.0001269	0.0194907	Myosin-6
P29622	-1.862155	0.2991501	9.385413	-6.224819	0.0001290	0.0194907	Kallistatin
Q06828	-4.135476	0.6523980	9.003303	-6.338886	0.0001344	0.0194907	Fibromodulin
P46821	-1.622963	0.2654404	9.385413	-6.114227	0.0001481	0.0200375	Microtubule-associated protein 1B;MAP1B heavy chain;MAP1 light chain LC1
P28066	-2.170776	0.3390487	8.500773	-6.402548	0.0001604	0.0203510	Proteasome subunit alpha type-5
Q9UGT4	-2.466535	0.4090800	9.193722	-6.029468	0.0001792	0.0213941	Sushi domain-containing protein 2
Q6PCB0	-2.300792	0.3926118	9.198450	-5.860221	0.0002211	0.0249365	von Willebrand factor A domain-containing protein 1
P35625	-3.979204	0.6344156	7.962134	-6.272235	0.0002447	0.0261405	Metalloproteinase inhibitor 3
P60468	-2.454190	0.4052019	8.241407	-6.056708	0.0002697	0.0268819	Protein transport protein Sec61 subunit beta
Q15327	-2.221783	0.3961366	9.280457	-5.608627	0.0002957	0.0268819	Ankyrin repeat domain-containing protein 1
Q14764	-1.616256	0.2901417	9.385413	-5.570573	0.0002985	0.0268819	Major vault protein
Q69YU5	3.220843	0.5625486	8.841525	5.725448	0.0003046	0.0268819	Uncharacterized protein C12orf73
Q9P2B2	-2.045271	0.3731311	9.385413	-5.481374	0.0003362	0.0281811	Prostaglandin F2 receptor negative regulator
P48163	-2.953929	0.4964480	7.960353	-5.950127	0.0003486	0.0281811	NADP-dependent malic enzyme
Q92930	-2.803127	0.4638105	7.597170	-6.043690	0.0003777	0.0281811	Ras-related protein Rab-8B
P48681	-1.493328	0.2771541	9.321612	-5.388078	0.0003901	0.0281811	Nestin
P01031	-1.652659	0.2888520	8.183937	-5.721472	0.0004077	0.0281811	Complement C5;Complement C5 beta chain;Complement C5 alpha chain;C5a anaphylatoxin;Complement C5 alpha chain
O43677	-2.965485	0.5101963	7.933870	-5.812438	0.0004121	0.0281811	NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
P02775	-2.169029	0.4075050	9.385413	-5.322705	0.0004165	0.0281811	Platelet basic protein;Connective tissue-activating peptide III;TC-2;Connective tissue-activating peptide III(1-81);Beta-thromboglobulin;Neutrophil-activating peptide 2(74);Neutrophil-activating peptide 2(73);Neutrophil-activating peptide 2;TC-1;Neutrophil-activating peptide 2(1-66);Neutrophil-activating peptide 2(1-63)
P30711	-2.323525	0.4343764	9.018645	-5.349105	0.0004597	0.0301015	Glutathione S-transferase theta-1
Q96FN9	-2.647962	0.4831404	8.385413	-5.480729	0.0004988	0.0308425	Probable D-tyrosyl-tRNA(Tyr) deacylase 2
P11586	2.011996	0.3618415	7.881516	5.560434	0.0005632	0.0308425	C-1-tetrahydrofolate synthase, cytoplasmic;Methylenetetrahydrofolate dehydrogenase;Methenyltetrahydrofolate cyclohydrolase;Formyltetrahydrofolate synthetase;C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
Q9H1K0	-2.283648	0.3962045	7.385413	-5.763812	0.0005668	0.0308425	Rabenosyn-5
P30405	-1.828202	0.3587630	9.385413	-5.095848	0.0005693	0.0308425	Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Q09161	2.423061	0.3818259	6.358037	6.345983	0.0005705	0.0308425	Nuclear cap-binding protein subunit 1
Q5NDL2	-2.704579	0.5131644	8.686198	-5.270394	0.0005771	0.0308425	EGF domain-specific O-linked N-acetylglucosamine transferase
Q9BZH6	3.420486	0.6371741	8.367230	5.368213	0.0005773	0.0308425	WD repeat-containing protein 11
O00180	-4.755346	0.8920012	8.385413	-5.331098	0.0006003	0.0309185	Potassium channel subfamily K member 1
P00748	-1.948996	0.3807404	9.091376	-5.118963	0.0006092	0.0309185	Coagulation factor XII;Coagulation factor XIIa heavy chain;Beta-factor XIIa part 1;Coagulation factor XIIa light chain
Q00G26	1.936681	0.3542707	7.788675	5.466670	0.0006541	0.0319953	Perilipin-5
P23142	-2.819044	0.5094029	7.590129	-5.534018	0.0006620	0.0319953	Fibulin-1
P10916	2.903591	0.5190748	7.385413	5.593783	0.0006814	0.0321678	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
Q9UHG2	-3.305283	0.6492888	8.796297	-5.090620	0.0007015	0.0323665	ProSAAS;KEP;Big SAAS;Little SAAS;Big PEN-LEN;PEN;Little LEN;Big LEN
Q9BW30	-2.326316	0.4679439	9.049210	-4.971357	0.0007561	0.0336366	Tubulin polymerization-promoting protein family member 3
P18428	-1.701410	0.3439009	9.013977	-4.947385	0.0007905	0.0336366	Lipopolysaccharide-binding protein
Q5JPH6	3.243753	0.5340074	6.212234	6.074360	0.0007941	0.0336366	Probable glutamate–tRNA ligase, mitochondrial
Q9BUH6	-1.516414	0.3086486	9.115985	-4.913078	0.0008018	0.0336366	Protein PAXX
P12883	1.752389	0.3596357	9.255194	4.872678	0.0008119	0.0336366	Myosin-7
P35052	-1.955749	0.3694381	7.703314	-5.293847	0.0008301	0.0337017	Glypican-1;Secreted glypican-1
Q8N474	-2.161723	0.4158032	7.847514	-5.198911	0.0008754	0.0348447	Secreted frizzled-related protein 1
Q99983	-3.574620	0.6431377	6.904704	-5.558094	0.0008937	0.0348873	Osteomodulin
P04004	-1.932935	0.4008337	8.981078	-4.822288	0.0009496	0.0354254	Vitronectin;Vitronectin V65 subunit;Vitronectin V10 subunit;Somatomedin-B
P62857	-2.138437	0.4200464	7.956911	-5.090954	0.0009561	0.0354254	40S ribosomal protein S28
O15061	-1.702821	0.3601514	9.385413	-4.728071	0.0009598	0.0354254	Synemin
P08603	-1.493256	0.3168082	9.385413	-4.713438	0.0009804	0.0355379	Complement factor H
Q9NRG4	2.553079	0.5223003	8.385413	4.888143	0.0010578	0.0376713	N-lysine methyltransferase SMYD2
Q96KC8	-2.528784	0.5175266	8.321700	-4.886287	0.0010840	0.0379395	DnaJ homolog subfamily C member 1
P23434	1.413938	0.3062675	9.385413	4.616676	0.0011287	0.0383884	Glycine cleavage system H protein, mitochondrial
Q04760	2.216188	0.4645453	8.599181	4.770661	0.0011516	0.0383884	Lactoylglutathione lyase
P02452	-2.007037	0.4158054	8.367424	-4.826865	0.0011535	0.0383884	Collagen alpha-1(I) chain
P24298	1.963174	0.4165267	8.623072	4.713201	0.0012356	0.0398590	Alanine aminotransferase 1
Q15113	-1.988509	0.4330474	9.188121	-4.591895	0.0012370	0.0398590	Procollagen C-endopeptidase enhancer 1
P50453	-1.422449	0.3086989	9.052869	-4.607886	0.0012567	0.0398605	Serpin B9
P04275	-1.362325	0.2963324	8.991784	-4.597287	0.0012986	0.0405566	von Willebrand factor;von Willebrand antigen 2
Q7L4S7	-2.547761	0.5017188	7.157555	-5.078066	0.0013409	0.0412425	Protein ARMCX6
Q86WV6	-1.336643	0.2979661	9.239827	-4.485891	0.0014229	0.0424928	Stimulator of interferon genes protein
Q92604	-1.925795	0.4331202	9.345516	-4.446330	0.0014664	0.0424928	Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
Q9HCB6	-2.416374	0.5273097	8.648303	-4.582457	0.0014674	0.0424928	Spondin-1
P82663	-1.935089	0.4352236	9.302714	-4.446194	0.0014834	0.0424928	28S ribosomal protein S25, mitochondrial
Q6PI78	1.948479	0.4338791	9.040261	4.490835	0.0014919	0.0424928	Transmembrane protein 65
Q8TDB4	-2.860288	0.5377313	6.330306	-5.319177	0.0015176	0.0424928	Protein MGARP
P01611	-2.219411	0.5030754	9.385413	-4.411687	0.0015281	0.0424928	Ig kappa chain V-I region Wes
Q15274	-2.178586	0.4620144	7.757883	-4.715407	0.0016427	0.0426894	Nicotinate-nucleotide pyrophosphorylase [carboxylating]
P08294	-1.898191	0.4077813	7.979491	-4.654924	0.0016454	0.0426894	Extracellular superoxide dismutase [Cu-Zn]
Q9BSD7	2.950896	0.6028017	7.080846	4.895302	0.0017057	0.0426894	Cancer-related nucleoside-triphosphatase
Q9Y6X5	-1.544960	0.3471001	8.750753	-4.451051	0.0017123	0.0426894	Bis(5-adenosyl)-triphosphatase ENPP4
Q6YN16	1.546774	0.3546814	9.222955	4.361023	0.0017180	0.0426894	Hydroxysteroid dehydrogenase-like protein 2
P01303	-2.163300	0.4894155	8.890312	-4.420171	0.0017214	0.0426894	Pro-neuropeptide Y;Neuropeptide Y;C-flanking peptide of NPY
P51888	-1.946837	0.3954667	6.959924	-4.922884	0.0017365	0.0426894	Prolargin
P07360	-1.547962	0.3489250	8.752393	-4.436374	0.0017475	0.0426894	Complement component C8 gamma chain
P04350	-2.838038	0.5777244	6.967833	-4.912443	0.0017514	0.0426894	Tubulin beta-4A chain
P24844	-1.783615	0.4121116	9.330669	-4.327990	0.0017561	0.0426894	Myosin regulatory light polypeptide 9
Q9UL26	7.923835	1.7917216	8.784585	4.422470	0.0017665	0.0426894	Ras-related protein Rab-22A
P07357	-1.256415	0.2926092	9.290174	-4.293832	0.0018671	0.0445443	Complement component C8 alpha chain
Q8TBP6	-1.527281	0.3500100	8.851865	-4.363535	0.0018871	0.0445443	Solute carrier family 25 member 40
P04003	-1.392094	0.3246379	9.090898	-4.288144	0.0019793	0.0459247	C4b-binding protein alpha chain
Q6UWS5	1.776260	0.3726694	7.068224	4.766316	0.0019908	0.0459247	Protein PET117 homolog, mitochondrial
O15230	-1.351267	0.3157713	9.044210	-4.279259	0.0020293	0.0462856	Laminin subunit alpha-5
O14980	-1.048446	0.2497751	9.382448	-4.197561	0.0021118	0.0476331	Exportin-1
O94875-10	1.381826	0.3251982	8.958355	4.249182	0.0021677	0.0483561	Sorbin and SH3 domain-containing protein 2
P12814	-2.192490	0.5008954	8.144626	-4.377140	0.0022587	0.0493912	Alpha-actinin-1
P02743	-1.660711	0.3999916	9.385413	-4.151865	0.0022628	0.0493912	Serum amyloid P-component;Serum amyloid P-component(1-203)
Q9HAT2	1.866882	0.4480930	9.216677	4.166282	0.0023025	0.0497243	Sialate O-acetylesterase

4.5 Evaluate results average contrast \(\log_2 FC_{V-A}\)

4.5.1 Volcano-plot

volcanoAvg <- ggplot(rowData(pe[["proteinRobust"]])$"tissueV + 0.5 * locationR:tissueV",
                 aes(x = logFC, y = -log10(pval), color = adjPval < 0.05)) +
 geom_point(cex = 2.5) +
 scale_color_manual(values = alpha(c("black", "red"), 0.5)) + theme_minimal()
volcanoAvg

4.5.2 Heatmap

We first select the names of the proteins that were declared signficant.

sigNamesAvg <- rowData(pe[["proteinRobust"]])$"tissueV + 0.5 * locationR:tissueV" %>%
 rownames_to_column("proteinRobust") %>%
 filter(adjPval<0.05) %>%
 pull(proteinRobust)
heatmap(assay(pe[["proteinRobust"]])[sigNamesAvg, ])

There are 461 proteins significantly differentially expressed at the 5% FDR level.

rowData(pe[["proteinRobust"]])$"tissueV + 0.5 * locationR:tissueV" %>%
  cbind(.,rowData(pe[["proteinRobust"]])$Protein.names) %>%
  na.exclude %>%
  filter(adjPval<0.05) %>%
  arrange(pval) %>%
  knitr::kable(.)

	logFC	se	df	t	pval	adjPval	rowData(pe[[“proteinRobust”]])$Protein.names
P08590	6.4625112	0.2976280	9.117912	21.713386	0.0000000	0.0000074	Myosin light chain 3
P12883	3.0427569	0.2557724	9.255194	11.896344	0.0000006	0.0006551	Myosin-7
O75368	-2.0672256	0.1911057	9.251939	-10.817185	0.0000015	0.0007617	SH3 domain-binding glutamic acid-rich-like protein
P10916	4.9061329	0.3591470	7.385413	13.660515	0.0000017	0.0007617	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
Q6UWY5	-2.8614477	0.2723232	9.170135	-10.507543	0.0000020	0.0007617	Olfactomedin-like protein 1
P46821	-1.9028923	0.1876947	9.385413	-10.138230	0.0000023	0.0007617	Microtubule-associated protein 1B;MAP1B heavy chain;MAP1 light chain LC1
P06858	2.5622451	0.2524054	9.218266	10.151307	0.0000026	0.0007617	Lipoprotein lipase
P29622	-1.9885126	0.2115311	9.385413	-9.400570	0.0000044	0.0010675	Kallistatin
P05546	-1.8329275	0.1931907	9.198639	-9.487658	0.0000047	0.0010675	Heparin cofactor 2
P21810	-3.1872304	0.3151219	8.304055	-10.114278	0.0000059	0.0011366	Biglycan
P35442	-2.7706752	0.2792024	8.385413	-9.923538	0.0000064	0.0011366	Thrombospondin-2
P13533	-4.1989377	0.4579673	9.115028	-9.168640	0.0000067	0.0011366	Myosin-6
Q06828	-4.1723327	0.4703068	9.003303	-8.871513	0.0000096	0.0014958	Fibromodulin
Q8N474	-2.7331853	0.2795787	7.847514	-9.776084	0.0000115	0.0016658	Secreted frizzled-related protein 1
P02452	-2.6166150	0.2921724	8.367424	-8.955722	0.0000144	0.0018663	Collagen alpha-1(I) chain
Q9UGT4	-2.3750749	0.2867846	9.193722	-8.281739	0.0000147	0.0018663	Sushi domain-containing protein 2
O94875-10	1.8515322	0.2254187	8.958355	8.213746	0.0000184	0.0019441	Sorbin and SH3 domain-containing protein 2
Q16647	-2.1609826	0.2677306	9.156725	-8.071483	0.0000186	0.0019441	Prostacyclin synthase
Q14764	-1.6211158	0.2051612	9.385413	-7.901669	0.0000191	0.0019441	Major vault protein
A6NMZ7	-2.6666436	0.3375438	9.385413	-7.900140	0.0000192	0.0019441	Collagen alpha-6(VI) chain
O95865	-1.5774343	0.2030636	9.385413	-7.768178	0.0000220	0.0020570	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
Q9P2B2	-2.0463902	0.2638435	9.385413	-7.756076	0.0000223	0.0020570	Prostaglandin F2 receptor negative regulator
Q15113	-2.3717647	0.3035044	9.188121	-7.814597	0.0000237	0.0020912	Procollagen C-endopeptidase enhancer 1
P18428	-1.8519938	0.2405365	9.013977	-7.699428	0.0000298	0.0025169	Lipopolysaccharide-binding protein
P02776	-2.2952145	0.2665516	7.718405	-8.610771	0.0000319	0.0025481	Platelet factor 4;Platelet factor 4, short form
P24844	-2.1677081	0.2920895	9.330669	-7.421383	0.0000330	0.0025481	Myosin regulatory light polypeptide 9
Q9BW30	-2.5325002	0.3361911	9.049210	-7.532919	0.0000346	0.0025481	Tubulin polymerization-promoting protein family member 3
P54652	-2.1555836	0.2857710	9.007166	-7.543045	0.0000351	0.0025481	Heat shock-related 70 kDa protein 2
P00748	-1.9760261	0.2655421	9.091376	-7.441479	0.0000372	0.0025980	Coagulation factor XII;Coagulation factor XIIa heavy chain;Beta-factor XIIa part 1;Coagulation factor XIIa light chain
O43677	-2.8617874	0.3490622	7.933870	-8.198503	0.0000384	0.0025980	NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
P48681	-1.4117043	0.1954445	9.321612	-7.223044	0.0000413	0.0026554	Nestin
P51888	-2.5731928	0.2835498	6.959924	-9.074923	0.0000419	0.0026554	Prolargin
P02775	-2.0605776	0.2881496	9.385413	-7.151070	0.0000432	0.0026568	Platelet basic protein;Connective tissue-activating peptide III;TC-2;Connective tissue-activating peptide III(1-81);Beta-thromboglobulin;Neutrophil-activating peptide 2(74);Neutrophil-activating peptide 2(73);Neutrophil-activating peptide 2;TC-1;Neutrophil-activating peptide 2(1-66);Neutrophil-activating peptide 2(1-63)
P08294	-2.3273246	0.2968595	7.979491	-7.839819	0.0000512	0.0030425	Extracellular superoxide dismutase [Cu-Zn]
O00180	-4.4260339	0.5900034	8.385413	-7.501710	0.0000539	0.0030425	Potassium channel subfamily K member 1
P02743	-1.9672445	0.2828368	9.385413	-6.955406	0.0000540	0.0030425	Serum amyloid P-component;Serum amyloid P-component(1-203)
P14854	1.6832743	0.2271074	8.346841	7.411798	0.0000604	0.0031941	Cytochrome c oxidase subunit 6B1
Q5NDL2	-2.5211042	0.3501742	8.686198	-7.199572	0.0000610	0.0031941	EGF domain-specific O-linked N-acetylglucosamine transferase
Q92604	-2.0980384	0.3057458	9.345516	-6.862036	0.0000614	0.0031941	Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
P60468	-1.9885569	0.2703727	8.241407	-7.354874	0.0000683	0.0034653	Protein transport protein Sec61 subunit beta
P23083	-3.2749341	0.4122019	7.385413	-7.944976	0.0000714	0.0035334	Ig heavy chain V-I region V35
P30405	-1.6842375	0.2536837	9.385413	-6.639124	0.0000781	0.0037005	Peptidyl-prolyl cis-trans isomerase F, mitochondrial
P51884	-1.9277723	0.2600484	7.936878	-7.413128	0.0000784	0.0037005	Lumican
Q9ULL5-3	-2.2984552	0.3119661	7.893242	-7.367645	0.0000842	0.0037660	Proline-rich protein 12
P01031	-1.4875185	0.2092918	8.183937	-7.107390	0.0000905	0.0037660	Complement C5;Complement C5 beta chain;Complement C5 alpha chain;C5a anaphylatoxin;Complement C5 alpha chain
Q6PCB0	-1.8152862	0.2753405	9.198450	-6.592879	0.0000905	0.0037660	von Willebrand factor A domain-containing protein 1
Q8TBP6	-1.7102618	0.2536922	8.851865	-6.741483	0.0000914	0.0037660	Solute carrier family 25 member 40
Q53GQ0	-1.8232291	0.2797866	9.334954	-6.516498	0.0000926	0.0037660	Very-long-chain 3-oxoacyl-CoA reductase
P36955	-1.6946775	0.2459657	8.456893	-6.889895	0.0000966	0.0037660	Pigment epithelium-derived factor
O14980	-1.1393991	0.1766395	9.382448	-6.450420	0.0000980	0.0037660	Exportin-1
Q92508	3.5066909	0.4088131	6.385413	8.577735	0.0000980	0.0037660	Piezo-type mechanosensitive ion channel component 1
Q14195-2	-2.2588828	0.3476626	9.262403	-6.497341	0.0000982	0.0037660	Dihydropyrimidinase-related protein 3
P05997	-2.5339895	0.3799038	8.864434	-6.670083	0.0000983	0.0037660	Collagen alpha-2(V) chain
Q15327	-1.7881570	0.2788386	9.280457	-6.412874	0.0001077	0.0039884	Ankyrin repeat domain-containing protein 1
P00325	-1.5039787	0.2325735	9.141096	-6.466682	0.0001081	0.0039884	Alcohol dehydrogenase 1B
P35625	-2.9820031	0.4278849	7.962134	-6.969171	0.0001188	0.0043077	Metalloproteinase inhibitor 3
P07451	-1.2910732	0.2057778	9.385413	-6.274113	0.0001214	0.0043228	Carbonic anhydrase 3
P04004	-1.7834542	0.2780483	8.981078	-6.414189	0.0001244	0.0043267	Vitronectin;Vitronectin V65 subunit;Vitronectin V10 subunit;Somatomedin-B
P41240	-1.3613815	0.2127198	8.922337	-6.399880	0.0001302	0.0043267	Tyrosine-protein kinase CSK
Q69YU5	2.4923143	0.3874663	8.841525	6.432339	0.0001305	0.0043267	Uncharacterized protein C12orf73
Q8WWA0	-4.4480904	0.6626292	8.244689	-6.712790	0.0001313	0.0043267	Intelectin-1
P46060	-1.7409587	0.2624323	8.385413	-6.633934	0.0001321	0.0043267	Ran GTPase-activating protein 1
P28066	-1.6401936	0.2502063	8.500773	-6.555364	0.0001353	0.0043611	Proteasome subunit alpha type-5
O15230	-1.3831391	0.2198154	9.044210	-6.292275	0.0001393	0.0044015	Laminin subunit alpha-5
O95980	-1.9680314	0.2898803	7.980660	-6.789117	0.0001409	0.0044015	Reversion-inducing cysteine-rich protein with Kazal motifs
Q6YN16	1.5369703	0.2490340	9.222955	6.171729	0.0001483	0.0045619	Hydroxysteroid dehydrogenase-like protein 2
Q7L4S7	-2.1476054	0.2976126	7.157555	-7.216110	0.0001572	0.0046901	Protein ARMCX6
P04003	-1.4355734	0.2328336	9.090898	-6.165662	0.0001587	0.0046901	C4b-binding protein alpha chain
Q15274	-2.0534369	0.3025225	7.757883	-6.787717	0.0001608	0.0046901	Nicotinate-nucleotide pyrophosphorylase [carboxylating]
P04083	-1.3497192	0.2233143	9.385413	-6.044035	0.0001617	0.0046901	Annexin A1
P36021	-2.5372663	0.3952239	8.385413	-6.419821	0.0001670	0.0047747	Monocarboxylate transporter 8
Q9BXN1	-2.2900275	0.3712225	8.937487	-6.168882	0.0001698	0.0047874	Asporin
Q9Y6X5	-1.4781975	0.2387999	8.750753	-6.190111	0.0001809	0.0050078	Bis(5-adenosyl)-triphosphatase ENPP4
Q07954	-1.3233833	0.2224711	9.385413	-5.948564	0.0001826	0.0050078	Prolow-density lipoprotein receptor-related protein 1;Low-density lipoprotein receptor-related protein 1 85 kDa subunit;Low-density lipoprotein receptor-related protein 1 515 kDa subunit;Low-density lipoprotein receptor-related protein 1 intracellular domain
O75828	-1.5053475	0.2540246	9.385413	-5.925992	0.0001879	0.0050083	Carbonyl reductase [NADPH] 3
P12110	-1.6865779	0.2700881	8.535409	-6.244548	0.0001885	0.0050083	Collagen alpha-2(VI) chain
Q9UBG0	-1.6619433	0.2773921	9.131671	-5.991314	0.0001931	0.0050083	C-type mannose receptor 2
P04196	-1.6884017	0.2542452	7.683140	-6.640839	0.0001946	0.0050083	Histidine-rich glycoprotein
Q9NZ01	-1.8500678	0.3007922	8.691035	-6.150652	0.0001949	0.0050083	Very-long-chain enoyl-CoA reductase
P23434	1.2703798	0.2165638	9.385413	5.866076	0.0002029	0.0051267	Glycine cleavage system H protein, mitochondrial
P23142	-2.3359021	0.3515315	7.590129	-6.644929	0.0002046	0.0051267	Fibulin-1
Q92681	-1.8263794	0.2904491	8.133279	-6.288122	0.0002200	0.0054460	Regulatory solute carrier protein family 1 member 1
P07357	-1.2056635	0.2077663	9.290174	-5.802980	0.0002289	0.0055985	Complement component C8 alpha chain
P04275	-1.2082122	0.2055449	8.991784	-5.878095	0.0002362	0.0057087	von Willebrand factor;von Willebrand antigen 2
P49207	-1.3752484	0.2347644	8.970773	-5.857995	0.0002444	0.0058016	60S ribosomal protein L34
Q8TBQ9	-1.7430434	0.2824761	8.170120	-6.170588	0.0002458	0.0058016	Protein kish-A
Q9BUF5	-1.7774391	0.3096233	9.217423	-5.740650	0.0002555	0.0059622	Tubulin beta-6 chain
P50453	-1.2397969	0.2150088	9.052869	-5.766260	0.0002648	0.0060077	Serpin B9
Q5JPH6	3.3748852	0.4562924	6.212234	7.396321	0.0002665	0.0060077	Probable glutamate–tRNA ligase, mitochondrial
Q9BZH6	2.6758207	0.4457948	8.367230	6.002360	0.0002702	0.0060077	WD repeat-containing protein 11
P01024	-1.1496569	0.2015704	9.197920	-5.703501	0.0002702	0.0060077	Complement C3;Complement C3 beta chain;C3-beta-c;Complement C3 alpha chain;C3a anaphylatoxin;Acylation stimulating protein;Complement C3b alpha chain;Complement C3c alpha chain fragment 1;Complement C3dg fragment;Complement C3g fragment;Complement C3d fragment;Complement C3f fragment;Complement C3c alpha chain fragment 2
Q9HCB6	-2.1126269	0.3589347	8.648303	-5.885825	0.0002723	0.0060077	Spondin-1
Q86WV6	-1.2006082	0.2120678	9.239827	-5.661436	0.0002805	0.0061226	Stimulator of interferon genes protein
P30711	-1.7885395	0.3126012	9.018645	-5.721474	0.0002842	0.0061378	Glutathione S-transferase theta-1
Q9NRG4	2.3553762	0.3989134	8.385413	5.904480	0.0003002	0.0063497	N-lysine methyltransferase SMYD2
O60760	-2.2815940	0.3864378	8.385413	-5.904169	0.0003003	0.0063497	Hematopoietic prostaglandin D synthase
P62760	-1.8910941	0.3355983	9.120970	-5.634992	0.0003044	0.0063707	Visinin-like protein 1
P12814	-1.9593420	0.3281249	8.144626	-5.971329	0.0003113	0.0064488	Alpha-actinin-1
P24298	1.6321192	0.2831640	8.623072	5.763865	0.0003191	0.0065425	Alanine aminotransferase 1
Q9UQ35	-1.2479485	0.2265532	9.385413	-5.508412	0.0003242	0.0065816	Serine/arginine repetitive matrix protein 2
P14550	-1.3044364	0.2225655	8.301450	-5.860910	0.0003283	0.0065991	Alcohol dehydrogenase [NADP(+)]
O94919	-1.1546247	0.2088661	9.248102	-5.528061	0.0003329	0.0066246	Endonuclease domain-containing 1 protein
Q9Y3B4	-1.2989386	0.2361784	9.218746	-5.499820	0.0003494	0.0068655	Splicing factor 3B subunit 6
P49458	-1.9200693	0.3013686	7.120983	-6.371165	0.0003517	0.0068655	Signal recognition particle 9 kDa protein
Q9UNW9	3.3281626	0.6111632	9.054127	5.445620	0.0003996	0.0076489	RNA-binding protein Nova-2
P48163	-1.9140897	0.3290692	7.960353	-5.816679	0.0004050	0.0076489	NADP-dependent malic enzyme
Q5M9N0	-2.7847331	0.4916908	8.350040	-5.663586	0.0004057	0.0076489	Coiled-coil domain-containing protein 158
P02747	-1.8649499	0.3002262	7.138784	-6.211815	0.0004069	0.0076489	Complement C1q subcomponent subunit C
Q00G26	1.4536200	0.2477814	7.788675	5.866543	0.0004159	0.0077448	Perilipin-5
Q8WY22	-1.5477211	0.2756010	8.385413	-5.615805	0.0004231	0.0077538	BRI3-binding protein
Q9UHG2	-2.4417072	0.4457629	8.796297	-5.477592	0.0004240	0.0077538	ProSAAS;KEP;Big SAAS;Little SAAS;Big PEN-LEN;PEN;Little LEN;Big LEN
Q9ULC3	-1.4634583	0.2660801	8.669265	-5.500068	0.0004336	0.0078588	Ras-related protein Rab-23
P25940	-1.6268129	0.3026580	9.043783	-5.375087	0.0004401	0.0079054	Collagen alpha-3(V) chain
Q53GG5-2	-2.4390475	0.4404803	8.429675	-5.537246	0.0004569	0.0080899	PDZ and LIM domain protein 3
Q8WZA9	-1.1072814	0.2082637	9.101344	-5.316729	0.0004653	0.0080899	Immunity-related GTPase family Q protein
P07585	-2.1345776	0.4031029	9.163968	-5.295366	0.0004680	0.0080899	Decorin
O00264	-1.4169853	0.2667510	9.079390	-5.312014	0.0004721	0.0080899	Membrane-associated progesterone receptor component 1
Q53T59	-1.8337712	0.3208050	7.876061	-5.716155	0.0004722	0.0080899	HCLS1-binding protein 3
Q6SZW1	-2.0501728	0.3456301	7.385413	-5.931696	0.0004742	0.0080899	Sterile alpha and TIR motif-containing protein 1
Q9BS26	-1.1652487	0.2228454	9.249914	-5.228955	0.0004964	0.0083980	Endoplasmic reticulum resident protein 44
P01008	-1.5396740	0.2964219	9.310907	-5.194199	0.0005096	0.0085495	Antithrombin-III
Q9UKR5	-3.7435260	0.6964057	8.595465	-5.375496	0.0005225	0.0086032	Probable ergosterol biosynthetic protein 28
P14543	-1.3422700	0.2580050	9.204669	-5.202496	0.0005229	0.0086032	Nidogen-1
P08603	-1.1544473	0.2240173	9.385413	-5.153386	0.0005255	0.0086032	Complement factor H
Q92621	-1.2423196	0.2415233	9.385413	-5.143684	0.0005326	0.0086499	Nuclear pore complex protein Nup205
Q9BTV4	-1.6057405	0.3110895	9.284468	-5.161667	0.0005377	0.0086637	Transmembrane protein 43
P13671	-1.3648753	0.2664751	9.385413	-5.121963	0.0005489	0.0087744	Complement component C6
Q2TAA5	-1.1443503	0.2235983	9.249693	-5.117885	0.0005779	0.0091655	GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
Q12996	-1.4804805	0.2552304	7.207709	-5.800565	0.0005960	0.0093205	Cleavage stimulation factor subunit 3
P20774	-2.1010556	0.3896021	8.210882	-5.392824	0.0005969	0.0093205	Mimecan
Q9UJC5	-1.2259781	0.2425389	9.326832	-5.054769	0.0006146	0.0094299	SH3 domain-binding glutamic acid-rich-like protein 2
P01042	-2.0066697	0.3480072	7.210294	-5.766173	0.0006170	0.0094299	Kininogen-1;Kininogen-1 heavy chain;T-kinin;Bradykinin;Lysyl-bradykinin;Kininogen-1 light chain;Low molecular weight growth-promoting factor
O14967	-1.6369952	0.3092277	8.430438	-5.293818	0.0006179	0.0094299	Calmegin
Q16082	-1.3233427	0.2607936	9.207589	-5.074291	0.0006225	0.0094299	Heat shock protein beta-2
Q6PI78	1.5357334	0.3017719	9.040261	5.089054	0.0006457	0.0097101	Transmembrane protein 65
Q8TDB4	-2.3494772	0.3787763	6.330306	-6.202809	0.0006590	0.0097915	Protein MGARP
Q9HAT2	1.6055669	0.3192733	9.216677	5.028817	0.0006608	0.0097915	Sialate O-acetylesterase
Q9BUH6	-1.1106212	0.2210609	9.115985	-5.024051	0.0006878	0.0100890	Protein PAXX
Q9ULD0	-2.0151143	0.3202146	6.128068	-6.293011	0.0006908	0.0100890	2-oxoglutarate dehydrogenase-like, mitochondrial
Q14314	-1.9322639	0.3920483	9.382448	-4.928637	0.0007208	0.0104515	Fibroleukin
P45877	-0.9996304	0.2027328	9.343571	-4.930777	0.0007275	0.0104735	Peptidyl-prolyl cis-trans isomerase C
Q96H79	-2.1774013	0.3587038	6.334231	-6.070192	0.0007408	0.0105623	Zinc finger CCCH-type antiviral protein 1-like
P35052	-1.2875376	0.2389775	7.703314	-5.387694	0.0007440	0.0105623	Glypican-1;Secreted glypican-1
P11586	1.2680380	0.2388823	7.881516	5.308212	0.0007574	0.0106771	C-1-tetrahydrofolate synthase, cytoplasmic;Methylenetetrahydrofolate dehydrogenase;Methenyltetrahydrofolate cyclohydrolase;Formyltetrahydrofolate synthetase;C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
Q9HAV4	-1.6824690	0.3206960	7.987893	-5.246305	0.0007811	0.0109357	Exportin-5
P40261	-1.4339415	0.2942762	9.340024	-4.872774	0.0007907	0.0109462	Nicotinamide N-methyltransferase
P02790	-1.3244981	0.2724643	9.385413	-4.861179	0.0007927	0.0109462	Hemopexin
P19429	2.0691315	0.3954475	7.976624	5.232379	0.0007980	0.0109462	Troponin I, cardiac muscle
P34932	-0.8925962	0.1844794	9.385413	-4.838461	0.0008188	0.0111559	Heat shock 70 kDa protein 4
Q09161	2.0115745	0.3402010	6.358037	5.912900	0.0008442	0.0114245	Nuclear cap-binding protein subunit 1
Q15126	-1.0103044	0.2097310	9.342811	-4.817144	0.0008552	0.0114968	Phosphomevalonate kinase
P50479	-2.1200408	0.4140571	8.131897	-5.120165	0.0008621	0.0115130	PDZ and LIM domain protein 4
Q9NY15	-1.4835786	0.3089047	9.336638	-4.802707	0.0008747	0.0116049	Stabilin-1
Q86VP6	-1.3548284	0.2717978	8.542953	-4.984693	0.0008822	0.0116274	Cullin-associated NEDD8-dissociated protein 1
Q07507	-1.3153838	0.2587790	8.160106	-5.083039	0.0008935	0.0116274	Dermatopontin
O43175	-2.0775407	0.4307821	9.173117	-4.822719	0.0008937	0.0116274	D-3-phosphoglycerate dehydrogenase
P02461	-2.9357775	0.5844720	8.323445	-5.022957	0.0009077	0.0116274	Collagen alpha-1(III) chain
P01034	-1.4660858	0.3001221	8.837162	-4.884964	0.0009125	0.0116274	Cystatin-C
P28300	-1.4793279	0.2827310	7.649016	-5.232280	0.0009129	0.0116274	Protein-lysine 6-oxidase
P13667	-1.1046003	0.2299757	9.181460	-4.803117	0.0009164	0.0116274	Protein disulfide-isomerase A4
Q86VU5	1.3820110	0.2907797	9.385413	4.752776	0.0009261	0.0116774	Catechol O-methyltransferase domain-containing protein 1
O43143	-0.8972350	0.1881734	9.289616	-4.768130	0.0009321	0.0116801	Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX15
O95183	-1.4595318	0.3089309	9.371170	-4.724460	0.0009689	0.0120661	Vesicle-associated membrane protein 5
Q96CS3	-1.1904104	0.2496881	9.119924	-4.767590	0.0009819	0.0121212	FAS-associated factor 2
P06727	-1.0625381	0.2206360	8.884167	-4.815797	0.0009881	0.0121212	Apolipoprotein A-IV
P09619	-1.2925211	0.2721302	9.154490	-4.749643	0.0009967	0.0121212	Platelet-derived growth factor receptor beta
P26447	-1.5232285	0.3150582	8.774968	-4.834753	0.0009972	0.0121212	Protein S100-A4
P46940	-1.1176083	0.2393244	9.306592	-4.669847	0.0010683	0.0129091	Ras GTPase-activating-like protein IQGAP1
Q15582	-2.2755713	0.4543685	7.899813	-5.008206	0.0010822	0.0129993	Transforming growth factor-beta-induced protein ig-h3
Q96JB2	-1.9983947	0.4070184	8.142504	-4.909838	0.0011200	0.0133746	Conserved oligomeric Golgi complex subunit 3
P01019	-1.0245069	0.2195559	9.093510	-4.666269	0.0011427	0.0135650	Angiotensinogen;Angiotensin-1;Angiotensin-2;Angiotensin-3;Angiotensin-4;Angiotensin 1-9;Angiotensin 1-7;Angiotensin 1-5;Angiotensin 1-4
Q99983	-3.0353776	0.5731048	6.904704	-5.296374	0.0011784	0.0139082	Osteomodulin
Q96LL9	-1.2761049	0.2726611	8.842792	-4.680187	0.0012079	0.0140956	DnaJ homolog subfamily C member 30
Q9NRX4	1.3837621	0.3021988	9.339127	4.578979	0.0012082	0.0140956	14 kDa phosphohistidine phosphatase
O95486	-1.3108014	0.2851357	9.187800	-4.597114	0.0012278	0.0142428	Protein transport protein Sec24A
P62328	-1.4789049	0.2892444	7.220282	-5.112994	0.0012549	0.0144745	Thymosin beta-4;Hematopoietic system regulatory peptide
P02748	-1.2312031	0.2668957	8.865762	-4.613050	0.0013178	0.0151138	Complement component C9;Complement component C9a;Complement component C9b
P83916	-1.6679489	0.3077674	6.385413	-5.419511	0.0013357	0.0152331	Chromobox protein homolog 1
Q8WWQ0	-1.2921726	0.2873956	9.385413	-4.496147	0.0013478	0.0152848	PH-interacting protein
P00747	-0.8346905	0.1843299	9.172800	-4.528243	0.0013623	0.0153642	Plasminogen;Plasmin heavy chain A;Activation peptide;Angiostatin;Plasmin heavy chain A, short form;Plasmin light chain B
P27658	-1.6429540	0.3664317	9.385413	-4.483656	0.0013729	0.0153982	Collagen alpha-1(VIII) chain;Vastatin
O95445	-2.5390830	0.5603209	9.052359	-4.531480	0.0014023	0.0154891	Apolipoprotein M
Q9UBV8	-1.1721927	0.2568550	8.885488	-4.563635	0.0014048	0.0154891	Peflin
Q92930	-1.4926298	0.3053336	7.597170	-4.888521	0.0014055	0.0154891	Ras-related protein Rab-8B
O15118	-2.1251890	0.3964131	6.385413	-5.361047	0.0014158	0.0154891	Niemann-Pick C1 protein
P03950	-1.7958993	0.3814592	8.216113	-4.707972	0.0014192	0.0154891	Angiogenin
Q8NAT1	-0.8669596	0.1945741	9.385413	-4.455677	0.0014312	0.0155361	Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2
Q9Y287	-1.6263595	0.3659544	9.385413	-4.444159	0.0014559	0.0157204	Integral membrane protein 2B;BRI2, membrane form;BRI2 intracellular domain;BRI2C, soluble form;Bri23 peptide
Q7Z3T8	-1.3963655	0.3020251	8.413206	-4.623343	0.0014913	0.0159618	Zinc finger FYVE domain-containing protein 16
P62857	-1.3918700	0.2939084	7.956911	-4.735728	0.0014940	0.0159618	40S ribosomal protein S28
Q08945	-1.4241196	0.3089376	8.385413	-4.609731	0.0015322	0.0162239	FACT complex subunit SSRP1
P82663	-1.3644647	0.3087747	9.302714	-4.418965	0.0015444	0.0162239	28S ribosomal protein S25, mitochondrial
Q9BYN0	-1.2858687	0.2896091	9.180640	-4.440015	0.0015462	0.0162239	Sulfiredoxin-1
Q6UWS5	1.3552496	0.2719635	7.068224	4.983204	0.0015505	0.0162239	Protein PET117 homolog, mitochondrial
P54577	-1.0275324	0.2300731	8.964139	-4.466112	0.0015790	0.0163449	Tyrosine–tRNA ligase, cytoplasmic;Tyrosine–tRNA ligase, cytoplasmic, N-terminally processed
P00352	-1.1336794	0.2474061	8.402816	-4.582262	0.0015817	0.0163449	Retinal dehydrogenase 1
Q96FN9	-1.6915779	0.3690046	8.385413	-4.584165	0.0015862	0.0163449	Probable D-tyrosyl-tRNA(Tyr) deacylase 2
Q9UKX3	1.6936818	0.3854938	9.208912	4.393538	0.0016433	0.0168485	Myosin-13
Q9H1E5	-1.0100442	0.2319493	9.385413	-4.354590	0.0016644	0.0169760	Thioredoxin-related transmembrane protein 4
Q9BXV9	1.4127212	0.3218254	9.163202	4.389714	0.0016725	0.0169760	Uncharacterized protein C14orf142
P80723	-1.5225978	0.3278699	7.910668	-4.643908	0.0017078	0.0172483	Brain acid soluble protein 1
A5D6W6	-2.1874865	0.4705266	7.868778	-4.649017	0.0017207	0.0172842	Fat storage-inducing transmembrane protein 1
Q8IYI6	-0.9655844	0.2230263	9.385413	-4.329463	0.0017284	0.0172842	Exocyst complex component 8
P15924	0.9305974	0.2148943	9.350459	4.330490	0.0017409	0.0173234	Desmoplakin
O15061	-1.0942259	0.2546655	9.385413	-4.296719	0.0018158	0.0178238	Synemin
Q9UK22	-1.4762619	0.2882849	6.372396	-5.120844	0.0018178	0.0178238	F-box only protein 2
P07384	-0.8789740	0.2042255	9.333139	-4.303938	0.0018195	0.0178238	Calpain-1 catalytic subunit
P52907	-0.8481991	0.1972352	9.339311	-4.300445	0.0018263	0.0178238	F-actin-capping protein subunit alpha-1
Q04721	1.1127233	0.2577419	9.201253	4.317199	0.0018437	0.0178982	Neurogenic locus notch homolog protein 2;Notch 2 extracellular truncation;Notch 2 intracellular domain
Q8N142	1.0825486	0.2509220	9.201572	4.314284	0.0018515	0.0178982	Adenylosuccinate synthetase isozyme 1
O60262	-1.2355761	0.2771111	8.388576	-4.458775	0.0018804	0.0180907	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
Q96A65	-0.8662506	0.2035141	9.382448	-4.256465	0.0019311	0.0184915	Exocyst complex component 4
Q9NS69	-1.0714067	0.2476392	8.946979	-4.326483	0.0019416	0.0185043	Mitochondrial import receptor subunit TOM22 homolog
Q96CX2	-0.9012081	0.2113310	9.290787	-4.264439	0.0019510	0.0185072	BTB/POZ domain-containing protein KCTD12
Q6IC98	-0.9007405	0.2081057	8.888308	-4.328283	0.0019666	0.0185681	GRAM domain-containing protein 4
P62745	-1.2315256	0.2839409	8.788016	-4.337261	0.0019937	0.0186338	Rho-related GTP-binding protein RhoB
O00625	-1.1467230	0.2709208	9.385413	-4.232687	0.0020006	0.0186338	Pirin
P31323	-0.9308385	0.2186352	9.229929	-4.257496	0.0020011	0.0186338	cAMP-dependent protein kinase type II-beta regulatory subunit
P05455	-0.8673708	0.2037435	9.178555	-4.257171	0.0020275	0.0187940	Lupus La protein
P61009	-0.8913019	0.2048775	8.621704	-4.350413	0.0020468	0.0188867	Signal peptidase complex subunit 3
P62277	-1.3147062	0.3106711	9.269754	-4.231827	0.0020596	0.0189187	40S ribosomal protein S13
P19447	-1.6209348	0.3503038	7.385413	-4.627226	0.0020905	0.0191159	TFIIH basal transcription factor complex helicase XPB subunit
P13796	-0.8965848	0.2123820	9.058132	-4.221566	0.0022024	0.0198918	Plastin-2
P50991	-1.4847501	0.3465048	8.685140	-4.284934	0.0022089	0.0198918	T-complex protein 1 subunit delta
Q9H1K0	-1.6569316	0.3616836	7.385413	-4.581164	0.0022125	0.0198918	Rabenosyn-5
Q9UL18	-1.3355815	0.3024699	8.037138	-4.415585	0.0022146	0.0198918	Protein argonaute-1
O75489	0.9821574	0.2367724	9.385413	4.148107	0.0022758	0.0202641	NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
Q96C86	-0.8840200	0.2112887	9.145534	-4.183943	0.0022805	0.0202641	m7GpppX diphosphatase
Q9UBB5	1.4054756	0.2873545	6.385413	4.891086	0.0022976	0.0202641	Methyl-CpG-binding domain protein 2
Q04760	1.3888487	0.3250035	8.599181	4.273334	0.0022977	0.0202641	Lactoylglutathione lyase
Q12988	-1.0008329	0.2396145	9.134204	-4.176846	0.0023111	0.0202641	Heat shock protein beta-3
Q8N5M1	-1.3322320	0.3166085	8.937206	-4.207821	0.0023159	0.0202641	ATP synthase mitochondrial F1 complex assembly factor 2
Q6P1N0	-1.6664832	0.3563734	6.936107	-4.676227	0.0023268	0.0202725	Coiled-coil and C2 domain-containing protein 1A
Q96AG4	-1.0700845	0.2592741	9.385413	-4.127233	0.0023497	0.0203023	Leucine-rich repeat-containing protein 59
Q07065	-0.9428402	0.2242953	8.903162	-4.203566	0.0023503	0.0203023	Cytoskeleton-associated protein 4
Q9Y4W6	0.9288317	0.2250637	9.237547	4.126973	0.0024317	0.0209168	AFG3-like protein 2
P00492	-0.9748591	0.2342661	8.867949	-4.161333	0.0025227	0.0215202	Hypoxanthine-guanine phosphoribosyltransferase
Q8IYU8	-3.0517638	0.6353282	6.385413	-4.803445	0.0025231	0.0215202	Calcium uptake protein 2, mitochondrial
O75348	-1.2953207	0.3178560	9.377764	-4.075181	0.0025496	0.0216557	V-type proton ATPase subunit G 1
Q9UKS6	0.9838252	0.2380314	8.943424	4.133174	0.0025822	0.0218407	Protein kinase C and casein kinase substrate in neurons protein 3
P50238	-1.7738249	0.4308810	8.850185	-4.116739	0.0027058	0.0227914	Cysteine-rich protein 1
P04843	-1.5463708	0.3734394	8.660976	-4.140889	0.0027359	0.0228771	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1
P05543	-1.2021068	0.2678425	7.101585	-4.488111	0.0027385	0.0228771	Thyroxine-binding globulin
Q96GK7	-1.2685155	0.2966639	7.917392	-4.275936	0.0027676	0.0230170	Fumarylacetoacetate hydrolase domain-containing protein 2A
P25311	-1.0760599	0.2606542	8.673237	-4.128305	0.0027779	0.0230170	Zinc-alpha-2-glycoprotein
Q9Y490	-0.8565056	0.2115741	9.149741	-4.048254	0.0027957	0.0230644	Talin-1
P58546	-1.2877434	0.3138586	8.783206	-4.102941	0.0028064	0.0230644	Myotrophin
P53618	-0.9257503	0.2314827	9.385413	-3.999220	0.0028622	0.0234285	Coatomer subunit beta
P28070	-0.9313857	0.2219436	8.111747	-4.196497	0.0029195	0.0237512	Proteasome subunit beta type-4
Q9NNX1	3.4364699	0.7363292	6.385413	4.667030	0.0029250	0.0237512	Tuftelin
Q9BXF6	-0.9435750	0.2370306	9.385413	-3.980816	0.0029451	0.0238189	Rab11 family-interacting protein 5
Q14118	-0.8636209	0.2063191	8.111452	-4.185849	0.0029629	0.0238356	Dystroglycan;Alpha-dystroglycan;Beta-dystroglycan
P21980	-0.9931919	0.2428774	8.618924	-4.089273	0.0029798	0.0238356	Protein-glutamine gamma-glutamyltransferase 2
P50552	-0.9356255	0.2329598	9.074476	-4.016253	0.0029847	0.0238356	Vasodilator-stimulated phosphoprotein
Q92575	-1.0319247	0.2532376	8.685218	-4.074927	0.0029941	0.0238356	UBX domain-containing protein 4
Q01581	-1.6309708	0.3718001	7.186730	-4.386687	0.0030119	0.0238838	Hydroxymethylglutaryl-CoA synthase, cytoplasmic
P31994-2	-0.8401092	0.2094556	8.992524	-4.010918	0.0030648	0.0242083	Low affinity immunoglobulin gamma Fc region receptor II-b
O75165	-0.7960642	0.1998267	9.132663	-3.983773	0.0030957	0.0242617	DnaJ homolog subfamily C member 13
Q9HB40	-1.4975944	0.3192059	6.179009	-4.691625	0.0031056	0.0242617	Retinoid-inducible serine carboxypeptidase
Q00577	-1.0160743	0.2542684	9.027366	-3.996069	0.0031099	0.0242617	Transcriptional activator protein Pur-alpha
O15031	-0.9218013	0.2310329	9.055589	-3.989914	0.0031194	0.0242617	Plexin-B2
P14625	-0.9806254	0.2486476	9.333808	-3.943837	0.0031532	0.0244236	Endoplasmin
Q7L4E1	-1.9857976	0.4950092	8.847472	-4.011637	0.0031642	0.0244236	Protein FAM73B
A6NDG6	1.0861342	0.2722626	8.937374	3.989289	0.0032057	0.0246261	Phosphoglycolate phosphatase
Q15125	-1.5304848	0.3855947	9.041599	-3.969154	0.0032291	0.0246261	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
Q2TAY7	-1.0799883	0.2732212	9.123335	-3.952799	0.0032522	0.0246261	WD40 repeat-containing protein SMU1;WD40 repeat-containing protein SMU1, N-terminally processed
E5RK69	-1.1331593	0.2897068	9.385413	-3.911400	0.0032812	0.0246261	Annexin
Q14258	-1.0273754	0.2506553	8.157903	-4.098758	0.0033032	0.0246261	E3 ubiquitin/ISG15 ligase TRIM25
Q9NS86	-1.0079781	0.2479673	8.316103	-4.064963	0.0033269	0.0246261	LanC-like protein 2
Q02818	-1.1109599	0.2603296	7.340441	-4.267513	0.0033293	0.0246261	Nucleobindin-1
P43121	-1.0927918	0.2720489	8.594930	-4.016894	0.0033306	0.0246261	Cell surface glycoprotein MUC18
Q7KZF4	-0.8983119	0.2302334	9.385413	-3.901744	0.0033311	0.0246261	Staphylococcal nuclease domain-containing protein 1
Q9Y2D4	-1.5301277	0.3819079	8.653139	-4.006536	0.0033354	0.0246261	Exocyst complex component 6B
P01303	-1.4085709	0.3549264	8.890312	-3.968628	0.0033419	0.0246261	Pro-neuropeptide Y;Neuropeptide Y;C-flanking peptide of NPY
Q9BWJ5	-1.1951212	0.3064683	9.385413	-3.899657	0.0033420	0.0246261	Splicing factor 3B subunit 5
P49773	-0.9630558	0.2471701	9.385413	-3.896327	0.0033594	0.0246261	Histidine triad nucleotide-binding protein 1
Q15738	-1.1253828	0.2888439	9.385413	-3.896163	0.0033603	0.0246261	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating
P46063	-0.8051976	0.2054091	9.154885	-3.919971	0.0033970	0.0248052	ATP-dependent DNA helicase Q1
Q9HBL0	1.0970067	0.2708307	8.290796	4.050526	0.0034176	0.0248666	Tensin-1
O95810	-0.7367195	0.1898992	9.385413	-3.879528	0.0034489	0.0250047	Serum deprivation-response protein
Q8IUX7	-2.4425715	0.5075886	5.640778	-4.812108	0.0035035	0.0253101	Adipocyte enhancer-binding protein 1
Q9Y5U8	-2.4377353	0.6307150	9.327097	-3.865035	0.0035696	0.0256674	Mitochondrial pyruvate carrier 1
P14555	-3.1537863	0.7281822	6.867951	-4.331040	0.0035904	0.0256674	Phospholipase A2, membrane associated
Q96PK6	-0.9222337	0.2373986	9.148490	-3.884749	0.0035909	0.0256674	RNA-binding protein 14
Q9UHD9	-0.9017767	0.2318045	9.043824	-3.890247	0.0036397	0.0257977	Ubiquilin-2
Q96EM0	-1.2584685	0.3144044	8.309610	-4.002706	0.0036419	0.0257977	Trans-3-hydroxy-L-proline dehydratase
Q9HCN8	-0.8835166	0.2288465	9.253672	-3.860738	0.0036473	0.0257977	Stromal cell-derived factor 2-like protein 1
P07360	-0.9669760	0.2462742	8.752393	-3.926420	0.0036711	0.0258764	Complement component C8 gamma chain
P10109	0.8561493	0.2221550	9.243225	3.853837	0.0036944	0.0259004	Adrenodoxin, mitochondrial
Q9H4A6	-1.0469452	0.2719485	9.266844	-3.849793	0.0037001	0.0259004	Golgi phosphoprotein 3
P27695	-1.4992289	0.3923412	9.385413	-3.821237	0.0037793	0.0263153	DNA-(apurinic or apyrimidinic site) lyase;DNA-(apurinic or apyrimidinic site) lyase, mitochondrial
Q53FA7	1.3792842	0.3581051	9.140607	3.851619	0.0037853	0.0263153	Quinone oxidoreductase PIG3
Q9NQZ5	1.3063706	0.3399333	9.137333	3.843021	0.0038384	0.0265728	StAR-related lipid transfer protein 7, mitochondrial
Q9UQR1	-1.5901460	0.3824514	7.327082	-4.157773	0.0038485	0.0265728	Zinc finger protein 148
Q68DH5	-1.0294876	0.2612363	8.365194	-3.940828	0.0039282	0.0270311	LMBR1 domain-containing protein 2
P78406	-1.7207435	0.3887386	6.279703	-4.426479	0.0039782	0.0270918	mRNA export factor
P62312	-1.5890450	0.4091948	8.671810	-3.883346	0.0039851	0.0270918	U6 snRNA-associated Sm-like protein LSm6
P10643	-1.1553612	0.3037929	9.241403	-3.803121	0.0039995	0.0270918	Complement component C7
Q9BT09	-1.2257851	0.3203966	9.058668	-3.825837	0.0040051	0.0270918	Protein canopy homolog 3
Q6PCE3	-1.3823379	0.3363631	7.385413	-4.109659	0.0040266	0.0270918	Glucose 1,6-bisphosphate synthase
Q9BVC6	-1.1861599	0.3132913	9.341936	-3.786124	0.0040278	0.0270918	Transmembrane protein 109
P00488	-1.1640817	0.3067565	9.268393	-3.794807	0.0040304	0.0270918	Coagulation factor XIII A chain
Q3ZCW2	-1.4639580	0.3351832	6.410138	-4.367635	0.0040470	0.0271133	Galectin-related protein
Q96KP1	-1.0715375	0.2583008	7.188491	-4.148409	0.0040611	0.0271186	Exocyst complex component 2
P61925	1.3829061	0.3292482	6.953044	4.200194	0.0040956	0.0271960	cAMP-dependent protein kinase inhibitor alpha
Q9UNN8	-1.2626877	0.3237195	8.433185	-3.900561	0.0040995	0.0271960	Endothelial protein C receptor
O00299	-0.9207980	0.2441733	9.349959	-3.771084	0.0041180	0.0272298	Chloride intracellular channel protein 1
Q8IVD9	-0.9866036	0.2486289	7.962021	-3.968177	0.0041691	0.0274783	NudC domain-containing protein 3
O15121	-1.4079273	0.3728328	9.216343	-3.776297	0.0041910	0.0275334	Sphingolipid delta(4)-desaturase DES1
P04207	-1.4228021	0.3725405	8.861844	-3.819188	0.0042135	0.0275916	Ig kappa chain V-III region CLL
P24311	1.0701358	0.2851747	9.295713	3.752563	0.0042839	0.0279625	Cytochrome c oxidase subunit 7B, mitochondrial
O75663	-1.7379175	0.4581589	8.939622	-3.793263	0.0043137	0.0280667	TIP41-like protein
Q8NBF2	-0.8250417	0.2215677	9.379760	-3.723655	0.0044137	0.0285351	NHL repeat-containing protein 2
P61020	-0.8382949	0.2205335	8.768454	-3.801213	0.0044149	0.0285351	Ras-related protein Rab-5B
P60903	-0.8876449	0.2381638	9.333841	-3.727035	0.0044279	0.0285351	Protein S100-A10
P41208	-1.1263858	0.2999947	9.075440	-3.754686	0.0044552	0.0286207	Centrin-2
P20042	-0.8887367	0.2370873	9.065935	-3.748564	0.0045061	0.0287075	Eukaryotic translation initiation factor 2 subunit 2
P27169	-1.0504292	0.2769234	8.718029	-3.793212	0.0045159	0.0287075	Serum paraoxonase/arylesterase 1
Q08357	-1.2684736	0.3315172	8.463053	-3.826267	0.0045409	0.0287075	Sodium-dependent phosphate transporter 2
Q16204	-0.8049274	0.2138365	8.902922	-3.764218	0.0045433	0.0287075	Coiled-coil domain-containing protein 6
Q8WUM0	-0.7917468	0.2110572	8.990261	-3.751338	0.0045540	0.0287075	Nuclear pore complex protein Nup133
P00918	-0.9510512	0.2547612	9.125781	-3.733109	0.0045623	0.0287075	Carbonic anhydrase 2
Q96MM6	1.7864789	0.4212053	6.459250	4.241349	0.0045992	0.0287075	Heat shock 70 kDa protein 12B
P31689	-1.4924000	0.3848993	8.072563	-3.877378	0.0046114	0.0287075	DnaJ homolog subfamily A member 1
P49756	-0.8931713	0.2418433	9.385413	-3.693182	0.0046276	0.0287075	RNA-binding protein 25
Q5JUQ0	2.7926112	0.6712936	6.726504	4.160044	0.0046289	0.0287075	Protein FAM78A
P01611	-1.3131481	0.3557280	9.385413	-3.691439	0.0046405	0.0287075	Ig kappa chain V-I region Wes
P32119	-0.9674030	0.2451869	7.636769	-3.945574	0.0046754	0.0287075	Peroxiredoxin-2
P62330	-0.8152583	0.2199163	9.196457	-3.707130	0.0046879	0.0287075	ADP-ribosylation factor 6
O75643	-0.7616501	0.2067379	9.385413	-3.684133	0.0046947	0.0287075	U5 small nuclear ribonucleoprotein 200 kDa helicase
P17050	-0.9853240	0.2652090	9.121362	-3.715273	0.0046949	0.0287075	Alpha-N-acetylgalactosaminidase
P31949	-0.9787100	0.2647594	9.277157	-3.696602	0.0046950	0.0287075	Protein S100-A11;Protein S100-A11, N-terminally processed
Q9Y646	-0.7162308	0.1940218	9.210822	-3.691497	0.0047915	0.0291484	Carboxypeptidase Q
Q1KMD3	-0.9795111	0.2640085	9.051770	-3.710149	0.0047958	0.0291484	Heterogeneous nuclear ribonucleoprotein U-like protein 2
Q6ZVF9	-1.5028535	0.3517719	6.221356	-4.272239	0.0048341	0.0292737	G protein-regulated inducer of neurite outgrowth 3
Q9BU61	-1.2998963	0.3549162	9.385413	-3.662545	0.0048588	0.0292737	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3
Q9Y5U9	-0.9729708	0.2545202	8.183105	-3.822764	0.0048597	0.0292737	Immediate early response 3-interacting protein 1
Q8TCJ2	-0.9004011	0.2429306	8.907652	-3.706413	0.0049600	0.0297891	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3B
Q15493	-1.6077032	0.4360378	9.046599	-3.687073	0.0049758	0.0297963	Regucalcin
Q9UBS4	-1.7446965	0.4698184	8.803956	-3.713555	0.0050071	0.0298953	DnaJ homolog subfamily B member 11
Q9BVG4	-1.4704698	0.4039345	9.385413	-3.640367	0.0050337	0.0299660	Protein PBDC1
O15144	-1.0444705	0.2843210	9.070426	-3.673560	0.0050589	0.0299983	Actin-related protein 2/3 complex subunit 2
Q9BXR6	-1.3501527	0.3714481	9.382448	-3.634835	0.0050810	0.0299983	Complement factor H-related protein 5
O43290	-0.7923809	0.2180343	9.385413	-3.634203	0.0050835	0.0299983	U4/U6.U5 tri-snRNP-associated protein 1
Q04837	-1.2562850	0.3379135	8.636848	-3.717771	0.0051451	0.0302738	Single-stranded DNA-binding protein, mitochondrial
O00567	-1.5854812	0.4377198	9.376799	-3.622138	0.0051902	0.0304511	Nucleolar protein 56
Q04941	-1.3384979	0.3673776	9.127049	-3.643385	0.0052480	0.0307016	Proteolipid protein 2
Q6P1L8	0.6869586	0.1895585	9.186165	3.623993	0.0053529	0.0312208	39S ribosomal protein L14, mitochondrial
P21281	-1.3587904	0.3769568	9.344431	-3.604631	0.0053675	0.0312208	V-type proton ATPase subunit B, brain isoform
Q8TDB6	-0.9160565	0.2529440	9.153547	-3.621578	0.0054049	0.0312627	E3 ubiquitin-protein ligase DTX3L
P56199	-0.9018380	0.2448251	8.647866	-3.683600	0.0054055	0.0312627	Integrin alpha-1
Q8IWU2	-0.7746135	0.2080306	8.224391	-3.723556	0.0055613	0.0319924	Serine/threonine-protein kinase LMTK2
Q9Y623	-2.1252883	0.5700777	8.189261	-3.728068	0.0055670	0.0319924	Myosin-4
P46777	-1.0470686	0.2879004	8.852405	-3.636912	0.0055790	0.0319924	60S ribosomal protein L5
Q96PE7	-1.1531979	0.3230087	9.385413	-3.570176	0.0056319	0.0321622	Methylmalonyl-CoA epimerase, mitochondrial
Q6ICB0	-2.0977670	0.5236139	6.696096	-4.006324	0.0056403	0.0321622	Desumoylating isopeptidase 1
P30050	-1.1234823	0.3143996	9.261423	-3.573421	0.0057230	0.0325424	60S ribosomal protein L12
P08754	-1.0611744	0.2984515	9.385413	-3.555601	0.0057651	0.0326906	Guanine nucleotide-binding protein G(k) subunit alpha
P11021	-0.7515167	0.2089700	8.970360	-3.596290	0.0058129	0.0328607	78 kDa glucose-regulated protein
P56192	-1.0557634	0.2923102	8.813819	-3.611792	0.0058414	0.0328607	Methionine–tRNA ligase, cytoplasmic
Q53GG5	1.0003784	0.2774742	8.865410	3.605302	0.0058437	0.0328607	PDZ and LIM domain protein 3
Q8NDY3	1.2195639	0.3410277	9.101142	3.576143	0.0058602	0.0328626	[Protein ADP-ribosylarginine] hydrolase-like protein 1
O75533	-0.7695176	0.2164213	9.256606	-3.555646	0.0058921	0.0329503	Splicing factor 3B subunit 1
P01699	-1.8429363	0.4533786	6.314916	-4.064895	0.0059388	0.0331204	Ig lambda chain V-I region VOR
Q14019	-2.4182957	0.5985491	6.385413	-4.040263	0.0059733	0.0331901	Coactosin-like protein
Q9Y5J7	-1.4119681	0.3997182	9.385413	-3.532409	0.0059840	0.0331901	Mitochondrial import inner membrane translocase subunit Tim9
P23284	-0.7777143	0.2189746	9.127890	-3.551619	0.0060629	0.0335357	Peptidyl-prolyl cis-trans isomerase B
Q9Y5Z7	-1.8906077	0.4616964	6.110612	-4.094916	0.0061500	0.0339251	Host cell factor 2
Q9HAV7	0.8784715	0.2455573	8.806708	3.577460	0.0061670	0.0339271	GrpE protein homolog 1, mitochondrial
P08670	-1.0385574	0.2890644	8.643328	-3.592824	0.0062100	0.0340714	Vimentin
Q9H9B4	-0.7835938	0.2188802	8.717170	-3.580012	0.0062456	0.0341738	Sideroflexin-1
Q5T447	-1.0539901	0.2946359	8.718056	-3.577263	0.0062709	0.0342204	E3 ubiquitin-protein ligase HECTD3
P05060	-2.3172970	0.6115268	7.305570	-3.789363	0.0062887	0.0342252	Secretogranin-1;PE-11;GAWK peptide;CCB peptide
P14174	-0.9252890	0.2597430	8.795118	-3.562324	0.0063263	0.0343378	Macrophage migration inhibitory factor
P00742	-1.3823666	0.3377126	6.021781	-4.093323	0.0063561	0.0343429	Coagulation factor X;Factor X light chain;Factor X heavy chain;Activated factor Xa heavy chain
P05062	-2.0691367	0.5491873	7.376614	-3.767634	0.0063611	0.0343429	Fructose-bisphosphate aldolase B
P01597	-2.2245190	0.6295868	8.995469	-3.533300	0.0063859	0.0343855	Ig kappa chain V-I region DEE
Q9UK41	-1.5840168	0.4525342	9.249370	-3.500325	0.0064436	0.0346045	Vacuolar protein sorting-associated protein 28 homolog
O14807	-1.0071551	0.2870529	9.142433	-3.508604	0.0064740	0.0346760	Ras-related protein M-Ras
Q9GZY4	-1.6315958	0.4423737	7.703311	-3.688275	0.0065660	0.0349087	Cytochrome c oxidase assembly factor 1 homolog
Q13011	0.8125674	0.2281934	8.603557	3.560872	0.0065690	0.0349087	Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial
A4D2B0	-1.7771506	0.4954576	8.385413	-3.586888	0.0065854	0.0349087	Metallo-beta-lactamase domain-containing protein 1
P27797	-0.8785716	0.2529576	9.382448	-3.473197	0.0065862	0.0349087	Calreticulin
Q9HAN9	1.2290381	0.3277463	7.306422	3.749968	0.0066297	0.0350474	Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
P02749	-1.0092251	0.2887067	9.025558	-3.495676	0.0067400	0.0355380	Beta-2-glycoprotein 1
Q14011	-1.6557884	0.4613486	8.231467	-3.589018	0.0067678	0.0355925	Cold-inducible RNA-binding protein
P62191	-0.9985121	0.2875705	9.176854	-3.472234	0.0068202	0.0357754	26S protease regulatory subunit 4
Q8NBJ5	-1.0369389	0.2922708	8.473099	-3.547871	0.0068666	0.0357787	Procollagen galactosyltransferase 1
P16455	-0.8416366	0.2363383	8.365652	-3.561152	0.0068706	0.0357787	Methylated-DNA–protein-cysteine methyltransferase
Q12907	-1.6608858	0.4654093	8.305704	-3.568657	0.0068737	0.0357787	Vesicular integral-membrane protein VIP36
Q9UMR3	-1.7064633	0.4609378	7.385413	-3.702155	0.0069386	0.0360239	T-box transcription factor TBX20
Q5VIR6-4	-0.9082357	0.2626254	9.130015	-3.458294	0.0070272	0.0363239	Vacuolar protein sorting-associated protein 53 homolog
P06396	-1.1602520	0.3284971	8.474042	-3.532001	0.0070322	0.0363239	Gelsolin
Q6Y288	-1.0921514	0.3170900	9.229532	-3.444295	0.0070709	0.0364313	Beta-1,3-glucosyltransferase
P98160	-0.7123685	0.2057393	9.004949	-3.462481	0.0071269	0.0366270	Basement membrane-specific heparan sulfate proteoglycan core protein;Endorepellin;LG3 peptide
Q9HCJ6	-0.9011150	0.2633086	9.382448	-3.422277	0.0071515	0.0366605	Synaptic vesicle membrane protein VAT-1 homolog-like
O43707	-1.3824302	0.3940398	8.555847	-3.508352	0.0071799	0.0367132	Alpha-actinin-4
Q13425	-0.7846763	0.2289447	9.241730	-3.427362	0.0072514	0.0369860	Beta-2-syntrophin
Q9UBI9	-1.9787149	0.5456575	7.613412	-3.626295	0.0073101	0.0371672	Headcase protein homolog
Q13636	-1.9278246	0.4828349	5.941397	-3.992720	0.0073236	0.0371672	Ras-related protein Rab-31
O43592	-0.8599780	0.2513274	9.208263	-3.421744	0.0073560	0.0372388	Exportin-T
P43686	-1.3071386	0.3842049	9.385413	-3.402192	0.0073848	0.0372913	26S protease regulatory subunit 6B
O75190-3	1.2139008	0.3579316	9.385413	3.391433	0.0075148	0.0378540	DnaJ homolog subfamily B member 6
Q9NX08	-0.7560262	0.2199925	8.886277	-3.436601	0.0075720	0.0379630	COMM domain-containing protein 8
Q96CN7	-1.0345528	0.3035605	9.151255	-3.408061	0.0075873	0.0379630	Isochorismatase domain-containing protein 1
O60568	-1.0499114	0.3101574	9.385413	-3.385092	0.0075926	0.0379630	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3
O60927	-0.9982244	0.2669526	6.797580	-3.739332	0.0076677	0.0381466	Protein phosphatase 1 regulatory subunit 11
Q9H2J4	-0.8634690	0.2556745	9.385413	-3.377220	0.0076903	0.0381466	Phosducin-like protein 3
Q8NFQ8	-0.7967626	0.2241386	7.843418	-3.554776	0.0077012	0.0381466	Torsin-1A-interacting protein 2
P15848	0.9063750	0.2622189	8.604816	3.456558	0.0077045	0.0381466	Arylsulfatase B
P30101	-0.7466004	0.2200397	9.129332	-3.393025	0.0077988	0.0385196	Protein disulfide-isomerase A3
P51692	-1.7183021	0.5058169	9.071768	-3.397083	0.0078195	0.0385280	Signal transducer and activator of transcription 5B
Q96LD4	-2.0992980	0.5326176	5.906119	-3.941473	0.0078555	0.0386116	Tripartite motif-containing protein 47
Q96G03	-0.8867606	0.2633690	9.330409	-3.366989	0.0078842	0.0386591	Phosphoglucomutase-2
P05387	-0.7376313	0.2197628	9.385413	-3.356488	0.0079539	0.0389072	60S acidic ribosomal protein P2
Q08AG7	-1.2342110	0.3426996	7.362325	-3.601437	0.0080096	0.0390851	Mitotic-spindle organizing protein 1
Q9Y678	-0.6484637	0.1937556	9.385413	-3.346813	0.0080802	0.0393350	Coatomer subunit gamma-1
P29992	-1.0188326	0.2947365	8.303781	-3.456757	0.0081310	0.0394877	Guanine nucleotide-binding protein subunit alpha-11
Q9BX97	-1.3844164	0.3942853	7.837641	-3.511205	0.0082107	0.0397799	Plasmalemma vesicle-associated protein
P16083	-1.0262131	0.3000391	8.385413	-3.420264	0.0084662	0.0409198	Ribosyldihydronicotinamide dehydrogenase [quinone]
P03915	-1.1707120	0.3448778	8.492156	-3.394570	0.0086415	0.0416682	NADH-ubiquinone oxidoreductase chain 5
Q13825	1.4155209	0.4286271	9.385413	3.302453	0.0086860	0.0417125	Methylglutaconyl-CoA hydratase, mitochondrial
P55735	-0.8920338	0.2672114	8.993847	-3.338307	0.0086918	0.0417125	Protein SEC13 homolog
Q13541	0.9219952	0.2801292	9.385413	3.291322	0.0088453	0.0423489	Eukaryotic translation initiation factor 4E-binding protein 1
Q9BSH5	-0.8053114	0.2432271	9.081702	-3.310944	0.0089588	0.0427913	Haloacid dehalogenase-like hydrolase domain-containing protein 3
O95159	-1.8090106	0.5289166	8.060595	-3.420219	0.0089825	0.0428040	Zinc finger protein-like 1
P61225	-0.7353323	0.2254094	9.385413	-3.262208	0.0092764	0.0440350	Ras-related protein Rap-2b
O75436	-1.0001875	0.2995476	8.574417	-3.338993	0.0092842	0.0440350	Vacuolar protein sorting-associated protein 26A
P22748	1.3439356	0.3988665	8.227398	3.369388	0.0094030	0.0444942	Carbonic anhydrase 4
O43920	0.7871398	0.2413857	9.266721	3.260921	0.0094526	0.0446249	NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
B0YJ81	-0.8197164	0.2437757	8.223227	-3.362585	0.0095069	0.0447771	Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1
P61026	-0.8525514	0.2469341	7.519029	-3.452546	0.0095312	0.0447877	Ras-related protein Rab-10
Q5VUM1	0.7593853	0.2321285	9.045228	3.271401	0.0095967	0.0449156	Succinate dehydrogenase assembly factor 4, mitochondrial
Q8N392	2.3525552	0.6309863	6.037587	3.728378	0.0096451	0.0449156	Rho GTPase-activating protein 18
Q8N129	-0.9589743	0.2874231	8.368916	-3.336456	0.0096458	0.0449156	Protein canopy homolog 4
P22897	-1.2570252	0.3866597	9.236964	-3.250986	0.0096469	0.0449156	Macrophage mannose receptor 1
I3L505	1.1736484	0.3548842	8.571534	3.307130	0.0097586	0.0453318	Acyl carrier protein
Q99459	-0.8211683	0.2419414	7.796908	-3.394079	0.0098104	0.0454681	Cell division cycle 5-like protein
Q13061	-2.4676439	0.7427573	8.281135	-3.322275	0.0100042	0.0462607	Triadin
Q9UBQ0	-1.1062507	0.3422745	9.158961	-3.232057	0.0100576	0.0464023	Vacuolar protein sorting-associated protein 29
P01621	-1.2058630	0.3710231	8.927861	-3.250102	0.0101023	0.0465026	Ig kappa chain V-III region NG9
O14656	-1.8276459	0.5541078	8.385413	-3.298358	0.0101964	0.0468296	Torsin-1A
P41743	-1.1383453	0.3178404	6.465679	-3.581500	0.0102399	0.0469233	Protein kinase C iota type
P09467	-1.3548161	0.3766861	6.379503	-3.596671	0.0102775	0.0469893	Fructose-1,6-bisphosphatase 1
P04430	-1.0635292	0.3314758	9.250027	-3.208467	0.0103183	0.0470701	Ig kappa chain V-I region BAN
Q9H4G4	-1.8410577	0.5694674	8.904758	-3.232947	0.0104175	0.0474158	Golgi-associated plant pathogenesis-related protein 1
P35754	0.7959584	0.2488883	9.268764	3.198055	0.0104680	0.0475244	Glutaredoxin-1
Q08211	-0.7008973	0.2199769	9.382448	-3.186232	0.0105108	0.0475244	ATP-dependent RNA helicase A
Q6UXG3	1.6056385	0.5021363	9.243547	3.197615	0.0105116	0.0475244	CMRF35-like molecule 9
Q9HD45	-0.9322808	0.2920818	9.281520	-3.191848	0.0105563	0.0476206	Transmembrane 9 superfamily member 3
O00487	-0.7979909	0.2500603	9.242344	-3.191194	0.0106238	0.0478188	26S proteasome non-ATPase regulatory subunit 14
Q86WH2	-1.4748731	0.3898450	5.524605	-3.783230	0.0106687	0.0479148	Ras association domain-containing protein 3
P08648	-0.9830382	0.3010637	8.373691	-3.265216	0.0107486	0.0481672	Integrin alpha-5;Integrin alpha-5 heavy chain;Integrin alpha-5 light chain
P07196	-3.1755881	0.8558310	5.733074	-3.710532	0.0108167	0.0483656	Neurofilament light polypeptide
P00156	-1.7108654	0.5393991	9.325104	-3.171799	0.0108447	0.0483803	Cytochrome b
P34947	-1.4297892	0.4514007	9.363114	-3.167450	0.0108677	0.0483803	G protein-coupled receptor kinase 5
Q6B0K9	-1.3489774	0.4080821	7.853752	-3.305652	0.0110508	0.0490876	Hemoglobin subunit mu
Q92616	-0.5950798	0.1874991	9.031070	-3.173775	0.0112487	0.0498578	Translational activator GCN1
Q92805	1.3236880	0.4166069	8.947665	3.177307	0.0113157	0.0499740	Golgin subfamily A member 1
Q14165	-1.0392026	0.3299855	9.277055	-3.149237	0.0113242	0.0499740	Malectin
P51665	-0.7776248	0.2465259	9.194991	-3.154333	0.0113529	0.0499924	26S proteasome non-ATPase regulatory subunit 7

4.6 Interaction

4.6.1 Volcano-plot

volcanoInt <- ggplot(rowData(pe[["proteinRobust"]])$"locationR:tissueV",
                 aes(x = logFC, y = -log10(pval), color = adjPval < 0.05)) +
 geom_point(cex = 2.5) +
 scale_color_manual(values = alpha(c("black", "red"), 0.5)) + theme_minimal()
volcanoInt

4.6.2 Heatmap

There were no genes significant at the 5% FDR level. We return the top 25 genes.

sigNamesInt <- rowData(pe[["proteinRobust"]])$"locationR:tissueV" %>%
 rownames_to_column("proteinRobust") %>%
 filter(adjPval<0.05) %>%
 pull(proteinRobust)
hlp <- order((rowData(pe[["proteinRobust"]])$"locationR:tissueV")[,"adjPval"])[1:25]
heatmap(assay(pe[["proteinRobust"]])[hlp, ])

There are 0 proteins significantly differentially expressed at the 5% FDR level.

rowData(pe[["proteinRobust"]])$"locationR:tissueV" %>%
  cbind(.,rowData(pe[["proteinRobust"]])$Protein.names) %>%
  na.exclude %>%
  filter(adjPval<0.05) %>%
  arrange(pval)

5 Large difference in number of proteins that are returned

Note, that much more proteins are returned significant for average contrast (\(\log_2 FC_{V-A}\)) as compared to contrast for assessing the fold change between ventriculum and atrium left and right. The power for the average contrast is larger than for the contrast left or right because the log2 FC can be estimated with higher precision.

For none of the proteins the interaction was significant (change in log2 FC between ventriculum and atrium in the right vs the left heart region). The power for the interaction is typically low.

5.1 Reason

Part of variance covariance matrix of model parameters due to design:

X <- model.matrix(~ location*tissue + patient, colData(pe))
covarUnscaled <- solve(t(X) %*% X)

Variance of contrasts (diagonal elements) due to design

varContrasts <- t(L)%*%covarUnscaled%*%L %>%
  diag
varContrasts

##                           tissueV       tissueV + locationR:tissueV 
##                         0.6666667                         0.6666667 
## tissueV + 0.5 * locationR:tissueV                 locationR:tissueV 
##                         0.3333333                         1.3333333

sqrt(varContrasts)

##                           tissueV       tissueV + locationR:tissueV 
##                         0.8164966                         0.8164966 
## tissueV + 0.5 * locationR:tissueV                 locationR:tissueV 
##                         0.5773503                         1.1547005

So it is clear that the standard error of the log2 FC left and right is the same. That of the average contrast is a factor \(\sqrt{2}\) smaller! Indeed, we use double the number of samples to estimate it!

varContrasts[3]/varContrasts[2]

## tissueV + 0.5 * locationR:tissueV 
##                               0.5

sqrt(varContrasts)[3]/sqrt(varContrasts)[2]

## tissueV + 0.5 * locationR:tissueV 
##                         0.7071068

1/sqrt(2)

## [1] 0.7071068

The standard error of the interaction is a factor \(\sqrt{2}\) larger than that of the main effects!

varContrasts[4]/varContrasts[2]

## locationR:tissueV 
##                 2

sqrt(varContrasts)[4]/sqrt(varContrasts)[2]

## locationR:tissueV 
##          1.414214

sqrt(2)

## [1] 1.414214

5.2 Msqrob

This is not the case for the standard errors of protein 2???

rowData(pe[["proteinRobust"]])$"tissueV"[2,]

rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV"[2,]

rowData(pe[["proteinRobust"]])$"tissueV + 0.5 * locationR:tissueV"[2,]

rowData(pe[["proteinRobust"]])$"locationR:tissueV"[2,]

Because msqrob is using robust regression to assess DE!

pe %>%
  colData %>%
  as_tibble %>%
  mutate(w=getModel(rowData(pe[["proteinRobust"]])$msqrobModels[[2]])$w)

For protein 2 the samples at the left and right side have different weights!

5.2.1 Part of standard error due to design:

covUnscaledRobust <- solve(
  t(X) %*%
  diag(
    getModel(rowData(pe[["proteinRobust"]])$msqrobModels[[2]])$w) %*% X)

varContrastsRobust <- t(L)%*%covUnscaledRobust%*%L %>%
  diag
varContrastsRobust

##                           tissueV       tissueV + locationR:tissueV 
##                         0.7187863                         0.8704210 
## tissueV + 0.5 * locationR:tissueV                 locationR:tissueV 
##                         0.3950893                         1.5980575

sqrt(varContrastsRobust)

##                           tissueV       tissueV + locationR:tissueV 
##                         0.8478127                         0.9329636 
## tissueV + 0.5 * locationR:tissueV                 locationR:tissueV 
##                         0.6285613                         1.2641430

5.2.2 Standard errors Contrasts

sqrt(varContrastsRobust) * getSigmaPosterior(rowData(pe[["proteinRobust"]])$msqrobModels[[2]])

##                           tissueV       tissueV + locationR:tissueV 
##                         0.5601628                         0.6164233 
## tissueV + 0.5 * locationR:tissueV                 locationR:tissueV 
##                         0.4153001                         0.8352387

rowData(pe[["proteinRobust"]])$"tissueV"[2,]

rowData(pe[["proteinRobust"]])$"tissueV + locationR:tissueV"[2,]

rowData(pe[["proteinRobust"]])$"tissueV + 0.5 * locationR:tissueV"[2,]

rowData(pe[["proteinRobust"]])$"locationR:tissueV"[2,]

5.3 Stagewise testing

5.3.1 Omnibus test

source("https://raw.githubusercontent.com/statOmics/SGA2020/gh-pages/assets/topFeaturesOmnibus.R")
pe <- omnibusTest(pe, "proteinRobust", L)

5.3.2 Heatmap significant proteins Omnibus test

We first select the names of the proteins that were declared signficant.

sigNamesOmnibus <- rowData(pe[["proteinRobust"]])$omnibusTest %>%
 rownames_to_column("proteinRobust") %>%
 filter(adjPval<0.05) %>%
 pull(proteinRobust)
heatmap(assay(pe[["proteinRobust"]])[sigNamesOmnibus, ])

There are 262 proteins significantly differentially expressed at the 5% FDR level.

rowData(pe[["proteinRobust"]])$omnibusTest  %>%
  cbind(.,rowData(pe[["proteinRobust"]])$Protein.names) %>%
  na.exclude %>%
  filter(adjPval<0.05) %>%
  arrange(pval) %>%
  knitr::kable(.)

	tissueV	tissueV…locationR.tissueV	tissueV…0.5…locationR.tissueV	locationR.tissueV	df1	df2	Fstat	pval	adjPval	rowData(pe[[“proteinRobust”]])$Protein.names
P08590	7.5669453	5.3580772	6.4625112	-2.2088680	2	9.117912	241.941690	0.0000000	0.0000255	Myosin light chain 3
P12883	4.3331248	1.7523890	3.0427569	-2.5807358	2	9.255194	82.809688	0.0000012	0.0012591	Myosin-7
P10916	6.9086744	2.9035913	4.9061329	-4.0050831	2	7.385413	107.580783	0.0000035	0.0023247	Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
O75368	-2.2903758	-1.8440754	-2.0672256	0.4463004	2	9.251939	59.046905	0.0000054	0.0023247	SH3 domain-binding glutamic acid-rich-like protein
P06858	1.7952437	3.3292464	2.5622451	1.5340027	2	9.218266	56.616101	0.0000066	0.0023247	Lipoprotein lipase
Q6UWY5	-3.2532286	-2.4696667	-2.8614477	0.7835619	2	9.170135	55.962919	0.0000073	0.0023247	Olfactomedin-like protein 1
P46821	-2.1828217	-1.6229630	-1.9028923	0.5598587	2	9.385413	52.504004	0.0000080	0.0023247	Microtubule-associated protein 1B;MAP1B heavy chain;MAP1 light chain LC1
P29622	-2.1148699	-1.8621552	-1.9885126	0.2527147	2	9.385413	44.363771	0.0000165	0.0039435	Kallistatin
P05546	-1.9156713	-1.7501838	-1.8329275	0.1654876	2	9.198639	45.181005	0.0000175	0.0039435	Heparin cofactor 2
P21810	-3.3802538	-2.9942069	-3.1872304	0.3860470	2	8.304055	51.174076	0.0000214	0.0042345	Biglycan
P35442	-2.3342598	-3.2070907	-2.7706752	-0.8728309	2	8.385413	49.249094	0.0000232	0.0042345	Thrombospondin-2
P13533	-4.3139246	-4.0839508	-4.1989377	0.2299738	2	9.115028	42.042011	0.0000250	0.0042345	Myosin-6
Q8N474	-3.3046470	-2.1617235	-2.7331853	1.1429234	2	7.847514	52.144823	0.0000294	0.0045872	Secreted frizzled-related protein 1
Q06828	-4.2091891	-4.1354763	-4.1723327	0.0737128	2	9.003303	39.385102	0.0000353	0.0051216	Fibromodulin
P02452	-3.2261931	-2.0070368	-2.6166150	1.2191563	2	8.367424	42.481732	0.0000415	0.0056136	Collagen alpha-1(I) chain
O95865	-2.1589316	-0.9959370	-1.5774343	1.1629946	2	9.385413	34.272459	0.0000486	0.0057994	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
O94875-10	2.3212380	1.3818264	1.8515322	-0.9394116	2	8.958355	36.659139	0.0000486	0.0057994	Sorbin and SH3 domain-containing protein 2
Q16647	-2.7876976	-1.5342676	-2.1609826	1.2534300	2	9.156725	34.947347	0.0000517	0.0058198	Prostacyclin synthase
Q9UGT4	-2.2836150	-2.4665348	-2.3750749	-0.1829198	2	9.193722	34.308942	0.0000545	0.0058198	Sushi domain-containing protein 2
P02776	-1.7487175	-2.8417114	-2.2952145	-1.0929939	2	7.718405	43.279869	0.0000639	0.0062978	Platelet factor 4;Platelet factor 4, short form
A6NMZ7	-2.2673287	-3.0659585	-2.6666436	-0.7986298	2	9.385413	31.905851	0.0000652	0.0062978	Collagen alpha-6(VI) chain
Q14764	-1.6259758	-1.6162557	-1.6211158	0.0097201	2	9.385413	31.218467	0.0000712	0.0065710	Major vault protein
Q15113	-2.7550209	-1.9885085	-2.3717647	0.7665124	2	9.188121	31.518143	0.0000770	0.0067277	Procollagen C-endopeptidase enhancer 1
Q9ULL5-3	-3.3863077	-1.2106027	-2.2984552	2.1757051	2	7.893242	39.193814	0.0000796	0.0067277	Proline-rich protein 12
Q9P2B2	-2.0475095	-2.0452709	-2.0463902	0.0022386	2	9.385413	30.078364	0.0000829	0.0067277	Prostaglandin F2 receptor negative regulator
P14854	2.3006633	1.0658853	1.6832743	-1.2347780	2	8.346841	33.671446	0.0001009	0.0075831	Cytochrome c oxidase subunit 6B1
P18428	-2.0025775	-1.7014100	-1.8519938	0.3011674	2	9.013977	29.954553	0.0001043	0.0075831	Lipopolysaccharide-binding protein
P54652	-1.5859216	-2.7252456	-2.1555836	-1.1393240	2	9.007166	29.940008	0.0001049	0.0075831	Heat shock-related 70 kDa protein 2
P24844	-2.5518015	-1.7836148	-2.1677081	0.7681867	2	9.330669	28.358116	0.0001083	0.0075831	Myosin regulatory light polypeptide 9
P51888	-3.1995487	-1.9468369	-2.5731928	1.2527118	2	6.959924	42.594973	0.0001247	0.0081957	Prolargin
Q9BW30	-2.7386840	-2.3263164	-2.5325002	0.4123676	2	9.049210	28.443735	0.0001252	0.0081957	Tubulin polymerization-promoting protein family member 3
O43677	-2.7580901	-2.9654848	-2.8617874	-0.2073947	2	7.933870	33.631479	0.0001335	0.0082984	NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
P00748	-2.0030563	-1.9489960	-1.9760261	0.0540602	2	9.091376	27.735769	0.0001349	0.0082984	Coagulation factor XII;Coagulation factor XIIa heavy chain;Beta-factor XIIa part 1;Coagulation factor XIIa light chain
P48681	-1.3300808	-1.4933277	-1.4117043	-0.1632468	2	9.321612	26.157695	0.0001501	0.0089644	Nestin
P02775	-1.9521262	-2.1690290	-2.0605776	-0.2169029	2	9.385413	25.639727	0.0001573	0.0090542	Platelet basic protein;Connective tissue-activating peptide III;TC-2;Connective tissue-activating peptide III(1-81);Beta-thromboglobulin;Neutrophil-activating peptide 2(74);Neutrophil-activating peptide 2(73);Neutrophil-activating peptide 2;TC-1;Neutrophil-activating peptide 2(1-66);Neutrophil-activating peptide 2(1-63)
P08294	-2.7564583	-1.8981910	-2.3273246	0.8582673	2	7.979491	31.192375	0.0001691	0.0090542	Extracellular superoxide dismutase [Cu-Zn]
P23083	-4.2742932	-2.2755749	-3.2749341	1.9987183	2	7.385413	35.088072	0.0001693	0.0090542	Ig heavy chain V-I region V35
P36955	-2.3236197	-1.0657353	-1.6946775	1.2578843	2	8.456893	28.729923	0.0001695	0.0090542	Pigment epithelium-derived factor
P02743	-2.2737781	-1.6607108	-1.9672445	0.6130673	2	9.385413	24.776129	0.0001801	0.0093742	Serum amyloid P-component;Serum amyloid P-component(1-203)
O00180	-4.0967217	-4.7553461	-4.4260339	-0.6586245	2	8.385413	28.272422	0.0001875	0.0095158	Potassium channel subfamily K member 1
P51884	-2.4022338	-1.4533109	-1.9277723	0.9489230	2	7.936878	29.702993	0.0002064	0.0099663	Lumican
P00325	-2.1088138	-0.8991435	-1.5039787	1.2096703	2	9.141096	24.684486	0.0002066	0.0099663	Alcohol dehydrogenase 1B
Q5NDL2	-2.3376295	-2.7045789	-2.5211042	-0.3669494	2	8.686198	25.916946	0.0002180	0.0099663	EGF domain-specific O-linked N-acetylglucosamine transferase
Q92604	-2.2702815	-1.9257953	-2.0980384	0.3444862	2	9.345516	23.715791	0.0002181	0.0099663	Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
Q53GQ0	-2.4308529	-1.2156054	-1.8232291	1.2152475	2	9.334954	23.651824	0.0002215	0.0099663	Very-long-chain 3-oxoacyl-CoA reductase
P60468	-1.5229242	-2.4541896	-1.9885569	-0.9312654	2	8.241407	27.348175	0.0002300	0.0099663	Protein transport protein Sec61 subunit beta
P07451	-1.8415388	-0.7406077	-1.2910732	1.1009311	2	9.385413	23.260186	0.0002307	0.0099663	Carbonic anhydrase 3
Q92508	4.0710006	2.9423812	3.5066909	-1.1286194	2	6.385413	40.291134	0.0002393	0.0101201	Piezo-type mechanosensitive ion channel component 1
Q6PCB0	-1.3297806	-2.3007919	-1.8152862	-0.9710113	2	9.198450	23.100847	0.0002591	0.0107360	von Willebrand factor A domain-containing protein 1
P28066	-1.1096114	-2.1707758	-1.6401936	-1.0611644	2	8.500773	25.051701	0.0002730	0.0108002	Proteasome subunit alpha type-5
Q9UBG0	-2.5762099	-0.7476767	-1.6619433	1.8285332	2	9.131671	22.977636	0.0002731	0.0108002	C-type mannose receptor 2
P30405	-1.5402735	-1.8282016	-1.6842375	-0.2879280	2	9.385413	22.200005	0.0002767	0.0108002	Peptidyl-prolyl cis-trans isomerase F, mitochondrial
P01031	-1.3223783	-1.6526586	-1.4875185	-0.3302802	2	8.183937	25.866283	0.0002898	0.0111012	Complement C5;Complement C5 beta chain;Complement C5 alpha chain;C5a anaphylatoxin;Complement C5 alpha chain
P05997	-3.0688637	-1.9991154	-2.5339895	1.0697482	2	8.864434	23.034598	0.0003082	0.0114681	Collagen alpha-2(V) chain
Q9ULD0	-0.5232010	-3.5070276	-2.0151143	-2.9838266	2	6.128068	39.648177	0.0003119	0.0114681	2-oxoglutarate dehydrogenase-like, mitochondrial
Q15327	-1.3545314	-2.2217826	-1.7881570	-0.8672512	2	9.280457	21.682263	0.0003179	0.0114681	Ankyrin repeat domain-containing protein 1
Q8TBP6	-1.8932428	-1.5272808	-1.7102618	0.3659619	2	8.851865	22.802350	0.0003220	0.0114681	Solute carrier family 25 member 40
Q14195-2	-2.5272781	-1.9904875	-2.2588828	0.5367907	2	9.262403	21.354010	0.0003397	0.0115202	Dihydropyrimidinase-related protein 3
P35625	-1.9848027	-3.9792035	-2.9820031	-1.9944008	2	7.962134	25.589243	0.0003412	0.0115202	Metalloproteinase inhibitor 3
O14980	-1.2303520	-1.0484463	-1.1393991	0.1819057	2	9.382448	20.935701	0.0003473	0.0115202	Exportin-1
Q8WWA0	-5.8069752	-3.0892056	-4.4480904	2.7177697	2	8.244689	24.246612	0.0003521	0.0115202	Intelectin-1
P46060	-1.9706423	-1.5112752	-1.7409587	0.4593671	2	8.385413	23.700667	0.0003543	0.0115202	Ran GTPase-activating protein 1
P36021	-3.1383009	-1.9362318	-2.5372663	1.2020690	2	8.385413	23.640542	0.0003575	0.0115202	Monocarboxylate transporter 8
Q69YU5	1.7637858	3.2208428	2.4923143	1.4570570	2	8.841525	21.866238	0.0003778	0.0119831	Uncharacterized protein C12orf73
O95980	-2.5524206	-1.3836422	-1.9680314	1.1687784	2	7.980660	24.630656	0.0003851	0.0120269	Reversion-inducing cysteine-rich protein with Kazal motifs
Q7L4S7	-1.7474498	-2.5477609	-2.1476054	-0.8003111	2	7.157555	27.778526	0.0004233	0.0128614	Protein ARMCX6
Q8TBQ9	-2.7618057	-0.7242810	-1.7430434	2.0375247	2	8.170120	23.247359	0.0004245	0.0128614	Protein kish-A
P04004	-1.6339729	-1.9329355	-1.7834542	-0.2989626	2	8.981078	20.612102	0.0004402	0.0128719	Vitronectin;Vitronectin V65 subunit;Vitronectin V10 subunit;Somatomedin-B
P12110	-2.1364562	-1.2366997	-1.6865779	0.8997564	2	8.535409	21.831782	0.0004403	0.0128719	Collagen alpha-2(VI) chain
P41240	-1.5691477	-1.1536153	-1.3613815	0.4155324	2	8.922337	20.715046	0.0004439	0.0128719	Tyrosine-protein kinase CSK
O15230	-1.4150113	-1.3512669	-1.3831391	0.0637444	2	9.044210	19.855982	0.0004913	0.0138534	Laminin subunit alpha-5
Q9NZ01	-2.3460403	-1.3540953	-1.8500678	0.9919450	2	8.691035	20.740126	0.0004914	0.0138534	Very-long-chain enoyl-CoA reductase
Q07954	-1.6748321	-0.9719344	-1.3233833	0.7028977	2	9.385413	18.940512	0.0005073	0.0140821	Prolow-density lipoprotein receptor-related protein 1;Low-density lipoprotein receptor-related protein 1 85 kDa subunit;Low-density lipoprotein receptor-related protein 1 515 kDa subunit;Low-density lipoprotein receptor-related protein 1 intracellular domain
Q9BXN1	-2.6709234	-1.9091316	-2.2900275	0.7617918	2	8.937487	19.871226	0.0005133	0.0140821	Asporin
Q15274	-1.9282879	-2.1785858	-2.0534369	-0.2502979	2	7.757883	23.240643	0.0005296	0.0141879	Nicotinate-nucleotide pyrophosphorylase [carboxylating]
Q6YN16	1.5271671	1.5467735	1.5369703	0.0196064	2	9.222955	19.046286	0.0005312	0.0141879	Hydroxysteroid dehydrogenase-like protein 2
P04083	-1.5245384	-1.1749000	-1.3497192	0.3496384	2	9.385413	18.571596	0.0005462	0.0143987	Annexin A1
P04003	-1.4790527	-1.3920940	-1.4355734	0.0869587	2	9.090898	19.007793	0.0005655	0.0147162	C4b-binding protein alpha chain
Q9UL18	-2.6023120	-0.0688510	-1.3355815	2.5334610	2	8.037138	21.366792	0.0006069	0.0154288	Protein argonaute-1
O60760	-3.5000288	-1.0631593	-2.2815940	2.4368695	2	8.385413	20.152153	0.0006268	0.0154288	Hematopoietic prostaglandin D synthase
Q9Y6X5	-1.4114347	-1.5449603	-1.4781975	-0.1335256	2	8.750753	19.161143	0.0006350	0.0154288	Bis(5-adenosyl)-triphosphatase ENPP4
P23142	-1.8527598	-2.8190443	-2.3359021	-0.9662845	2	7.590129	22.566639	0.0006390	0.0154288	Fibulin-1
Q92736-2	-3.3307404	1.0781855	-1.1262774	4.4089259	2	8.908498	18.724478	0.0006447	0.0154288	Ryanodine receptor 2
Q96LL9	-2.4266405	-0.1255693	-1.2761049	2.3010712	2	8.842792	18.847708	0.0006474	0.0154288	DnaJ homolog subfamily C member 30
O75828	-1.6417394	-1.3689557	-1.5053475	0.2727838	2	9.385413	17.702832	0.0006530	0.0154288	Carbonyl reductase [NADPH] 3
P04196	-1.9171807	-1.4596228	-1.6884017	0.4575579	2	7.683140	22.070959	0.0006536	0.0154288	Histidine-rich glycoprotein
P30711	-1.2535537	-2.3235254	-1.7885395	-1.0699717	2	9.018645	18.192306	0.0006834	0.0159469	Glutathione S-transferase theta-1
P23434	1.1268218	1.4139379	1.2703798	0.2871161	2	9.385413	17.425133	0.0006923	0.0159707	Glycine cleavage system H protein, mitochondrial
Q5JPH6	3.5060169	3.2437535	3.3748852	-0.2622634	2	6.212234	28.881640	0.0007149	0.0163056	Probable glutamate–tRNA ligase, mitochondrial
Q92681	-2.1530541	-1.4997046	-1.8263794	0.6533496	2	8.133279	19.834425	0.0007448	0.0167504	Regulatory solute carrier protein family 1 member 1
Q9BZH6	1.9311553	3.4204862	2.6758207	1.4893309	2	8.367230	19.171225	0.0007509	0.0167504	WD repeat-containing protein 11
P49207	-1.5348292	-1.2156675	-1.3752484	0.3191617	2	8.970773	17.586091	0.0007870	0.0173652	60S ribosomal protein L34
P07357	-1.1549122	-1.2564148	-1.2056635	-0.1015026	2	9.290174	16.879989	0.0008065	0.0174685	Complement component C8 alpha chain
P04275	-1.0540996	-1.3623248	-1.2082122	-0.3082252	2	8.991784	17.410957	0.0008089	0.0174685	von Willebrand factor;von Willebrand antigen 2
P48163	-0.8742508	-2.9539287	-1.9140897	-2.0796779	2	7.960353	19.749073	0.0008201	0.0175233	NADP-dependent malic enzyme
Q9NRG4	2.1576737	2.5530787	2.3553762	0.3954050	2	8.385413	18.346713	0.0008659	0.0182138	N-lysine methyltransferase SMYD2
Q9BUF5	-1.9343777	-1.6205004	-1.7774391	0.3138773	2	9.217423	16.653562	0.0008703	0.0182138	Tubulin beta-6 chain
P50453	-1.0571443	-1.4224494	-1.2397969	-0.3653051	2	9.052869	16.851253	0.0008877	0.0183877	Serpin B9
P40261	-2.3067271	-0.5611559	-1.4339415	1.7455712	2	9.340024	16.214682	0.0009165	0.0186174	Nicotinamide N-methyltransferase
O14967	-2.3931306	-0.8808598	-1.6369952	1.5122708	2	8.430438	17.938253	0.0009171	0.0186174	Calmegin
Q9HCB6	-1.8088797	-2.4163742	-2.1126269	-0.6074945	2	8.648303	17.394332	0.0009313	0.0186367	Spondin-1
Q86WV6	-1.0645731	-1.3366433	-1.2006082	-0.2720702	2	9.239827	16.281293	0.0009364	0.0186367	Stimulator of interferon genes protein
P01024	-1.1482973	-1.1510164	-1.1496569	-0.0027191	2	9.197920	16.269998	0.0009533	0.0187877	Complement C3;Complement C3 beta chain;C3-beta-c;Complement C3 alpha chain;C3a anaphylatoxin;Acylation stimulating protein;Complement C3b alpha chain;Complement C3c alpha chain fragment 1;Complement C3dg fragment;Complement C3g fragment;Complement C3d fragment;Complement C3f fragment;Complement C3c alpha chain fragment 2
Q8WZA9	-1.5022008	-0.7123621	-1.1072814	0.7898387	2	9.101344	16.199917	0.0010030	0.0192980	Immunity-related GTPase family Q protein
Q8WY22	-1.8394420	-1.2560002	-1.5477211	0.5834418	2	8.385413	17.535888	0.0010096	0.0192980	BRI3-binding protein
O00264	-1.9992421	-0.8347285	-1.4169853	1.1645136	2	9.079390	16.165900	0.0010187	0.0192980	Membrane-associated progesterone receptor component 1
P49458	-2.3208229	-1.5193157	-1.9200693	0.8015072	2	7.120983	20.998598	0.0010323	0.0192980	Signal recognition particle 9 kDa protein
Q00G26	0.9705589	1.9366811	1.4536200	0.9661222	2	7.788675	18.796138	0.0010453	0.0192980	Perilipin-5
P24298	1.3010640	1.9631743	1.6321192	0.6621103	2	8.623072	16.855736	0.0010485	0.0192980	Alanine aminotransferase 1
P12814	-1.7261945	-2.1924895	-1.9593420	-0.4662950	2	8.144626	17.867453	0.0010509	0.0192980	Alpha-actinin-1
P62760	-1.9296447	-1.8525435	-1.8910941	0.0771012	2	9.120970	15.908955	0.0010620	0.0192980	Visinin-like protein 1
Q92621	-1.7555813	-0.7290578	-1.2423196	1.0265235	2	9.385413	15.486770	0.0010647	0.0192980	Nuclear pore complex protein Nup205
P14550	-1.3940797	-1.2147931	-1.3044364	0.1792867	2	8.301450	17.330401	0.0010881	0.0195469	Alcohol dehydrogenase [NADP(+)]
Q9UHG2	-1.5781315	-3.3052829	-2.4417072	-1.7271515	2	8.796297	16.293511	0.0011019	0.0195842	ProSAAS;KEP;Big SAAS;Little SAAS;Big PEN-LEN;PEN;Little LEN;Big LEN
Q9UQ35	-1.3675109	-1.1283860	-1.2479485	0.2391249	2	9.385413	15.310560	0.0011095	0.0195842	Serine/arginine repetitive matrix protein 2
Q9UNW9	4.0970526	2.5592726	3.3281626	-1.5377800	2	9.054127	15.777880	0.0011203	0.0196049	RNA-binding protein Nova-2
P02747	-2.6809142	-1.0489855	-1.8649499	1.6319287	2	7.138784	20.155201	0.0011582	0.0200961	Complement C1q subcomponent subunit C
O94919	-1.1585816	-1.1506677	-1.1546247	0.0079139	2	9.248102	15.281924	0.0011709	0.0201441	Endonuclease domain-containing 1 protein
Q9UBB5	2.6733014	0.1376498	1.4054756	-2.5356516	2	6.385413	22.969050	0.0012118	0.0206722	Methyl-CpG-binding domain protein 2
Q9Y3B4	-1.2545628	-1.3433144	-1.2989386	-0.0887516	2	9.218746	15.129931	0.0012255	0.0207013	Splicing factor 3B subunit 6
Q92930	-0.1821330	-2.8031266	-1.4926298	-2.6209936	2	7.597170	18.350597	0.0012339	0.0207013	Ras-related protein Rab-8B
Q09161	1.6000882	2.4230607	2.0115745	0.8229726	2	6.358037	22.719676	0.0012705	0.0210567	Nuclear cap-binding protein subunit 1
Q9ULC3	-1.6748081	-1.2521086	-1.4634583	0.4226994	2	8.669265	15.832512	0.0012759	0.0210567	Ras-related protein Rab-23
Q5M9N0	-3.5370655	-2.0324007	-2.7847331	1.5046647	2	8.350040	16.314342	0.0013050	0.0213638	Coiled-coil domain-containing protein 158
Q6SZW1	-2.5636873	-1.5366583	-2.0501728	1.0270290	2	7.385413	18.512262	0.0013274	0.0215565	Sterile alpha and TIR motif-containing protein 1
Q53GG5-2	-2.9233739	-1.9547211	-2.4390475	0.9686528	2	8.429675	16.001178	0.0013491	0.0215717	PDZ and LIM domain protein 3
P31994-2	-1.6555661	-0.0246523	-0.8401092	1.6309138	2	8.992524	15.052398	0.0013496	0.0215717	Low affinity immunoglobulin gamma Fc region receptor II-b
P08603	-0.8156387	-1.4932560	-1.1544473	-0.6776173	2	9.385413	14.422402	0.0013730	0.0217748	Complement factor H
Q96FN9	-0.7351941	-2.6479617	-1.6915779	-1.9127675	2	8.385413	15.887535	0.0014054	0.0221164	Probable D-tyrosyl-tRNA(Tyr) deacylase 2
P11586	0.5240804	2.0119956	1.2680380	1.4879152	2	7.881516	16.870189	0.0014189	0.0221574	C-1-tetrahydrofolate synthase, cytoplasmic;Methylenetetrahydrofolate dehydrogenase;Methenyltetrahydrofolate cyclohydrolase;Formyltetrahydrofolate synthetase;C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
Q9H1K0	-1.0302150	-2.2836483	-1.6569316	-1.2534333	2	7.385413	18.059570	0.0014323	0.0221947	Rabenosyn-5
Q9BUH6	-0.7048278	-1.5164145	-1.1106212	-0.8115867	2	9.115985	14.547929	0.0014559	0.0223900	Protein PAXX
Q53T59	-1.8521243	-1.8154181	-1.8337712	0.0367062	2	7.876061	16.521863	0.0015200	0.0230978	HCLS1-binding protein 3
P25940	-1.6803001	-1.5733256	-1.6268129	0.1069744	2	9.043783	14.456074	0.0015247	0.0230978	Collagen alpha-3(V) chain
Q9NY15	-2.1774225	-0.7897346	-1.4835786	1.3876880	2	9.336638	14.011059	0.0015443	0.0232216	Stabilin-1
Q8NAT1	-1.4164507	-0.3174685	-0.8669596	1.0989822	2	9.385413	13.914217	0.0015581	0.0232449	Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2
O43464	-1.9007206	0.7261872	-0.5872667	2.6269078	2	9.072346	14.297299	0.0015687	0.0232449	Serine protease HTRA2, mitochondrial
P07585	-1.9272925	-2.3418627	-2.1345776	-0.4145702	2	9.163968	14.130035	0.0015853	0.0233194	Decorin
Q99983	-2.4961356	-3.5746196	-3.0353776	-1.0784839	2	6.904704	18.806830	0.0016058	0.0234514	Osteomodulin
Q9BS26	-1.2263582	-1.1041391	-1.1652487	0.1222191	2	9.249914	13.727711	0.0017043	0.0246056	Endoplasmic reticulum resident protein 44
Q9UKR5	-3.2086830	-4.2783690	-3.7435260	-1.0696861	2	8.595465	14.600416	0.0017210	0.0246056	Probable ergosterol biosynthetic protein 28
Q9HAV4	-2.2052737	-1.1596644	-1.6824690	1.0456093	2	7.987893	15.661958	0.0017212	0.0246056	Exportin-5
Q9BTV4	-1.8104632	-1.4010178	-1.6057405	0.4094454	2	9.284468	13.566939	0.0017561	0.0248698	Transmembrane protein 43
P35052	-0.6193263	-1.9557489	-1.2875376	-1.3364227	2	7.703314	16.101781	0.0017721	0.0248698	Glypican-1;Secreted glypican-1
P01008	-1.5471922	-1.5321558	-1.5396740	0.0150364	2	9.310907	13.489881	0.0017764	0.0248698	Antithrombin-III
P13671	-1.1914382	-1.5383124	-1.3648753	-0.3468742	2	9.385413	13.329057	0.0018101	0.0249035	Complement component C6
P14543	-1.3845506	-1.2999894	-1.3422700	0.0845612	2	9.204669	13.536114	0.0018145	0.0249035	Nidogen-1
Q12996	-1.6674028	-1.2935582	-1.4804805	0.3738446	2	7.207709	17.128176	0.0018261	0.0249035	Cleavage stimulation factor subunit 3
Q2TAA5	-1.3192452	-0.9694554	-1.1443503	0.3497898	2	9.249693	13.452203	0.0018279	0.0249035	GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
Q6PI78	1.1229874	1.9484794	1.5357334	0.8254920	2	9.040261	13.666187	0.0018499	0.0249839	Transmembrane protein 65
P01042	-2.2563158	-1.7570236	-2.0066697	0.4992922	2	7.210294	17.020705	0.0018584	0.0249839	Kininogen-1;Kininogen-1 heavy chain;T-kinin;Bradykinin;Lysyl-bradykinin;Kininogen-1 light chain;Low molecular weight growth-promoting factor
Q96H79	-3.0216701	-1.3331324	-2.1774013	1.6885377	2	6.334231	19.561690	0.0019464	0.0259943	Zinc finger CCCH-type antiviral protein 1-like
Q8TDB4	-1.8386665	-2.8602879	-2.3494772	-1.0216214	2	6.330306	19.494450	0.0019690	0.0261246	Protein MGARP
P45877	-1.2597920	-0.7394688	-0.9996304	0.5203232	2	9.343571	13.002295	0.0019971	0.0261892	Peptidyl-prolyl cis-trans isomerase C
P20774	-2.2367735	-1.9653377	-2.1010556	0.2714358	2	8.210882	14.549345	0.0019997	0.0261892	Mimecan
Q9HAT2	1.3442519	1.8668820	1.6055669	0.5226301	2	9.216677	13.044682	0.0020515	0.0266959	Sialate O-acetylesterase
Q9UJC5	-1.1262301	-1.3257262	-1.2259781	-0.1994961	2	9.326832	12.870624	0.0020783	0.0268689	SH3 domain-binding glutamic acid-rich-like protein 2
P34932	-1.1634292	-0.6217632	-0.8925962	0.5416660	2	9.385413	12.783000	0.0020913	0.0268689	Heat shock 70 kDa protein 4
Q9GZY4	-3.1677681	-0.0954235	-1.6315958	3.0723446	2	7.703311	15.142943	0.0021422	0.0271006	Cytochrome c oxidase assembly factor 1 homolog
Q96C86	-1.5155718	-0.2524683	-0.8840200	1.2631035	2	9.145534	12.949577	0.0021488	0.0271006	m7GpppX diphosphatase
Q16082	-1.3619821	-1.2847033	-1.3233427	0.0772788	2	9.207589	12.877393	0.0021494	0.0271006	Heat shock protein beta-2
Q96KC8	0.8980074	-2.5287840	-0.8153883	-3.4267914	2	8.321700	13.939197	0.0022045	0.0276241	DnaJ homolog subfamily C member 1
P56539	-2.0519177	0.6926641	-0.6796268	2.7445818	2	8.553679	13.356405	0.0023380	0.0291177	Caveolin-3
P62857	-0.6453035	-2.1384365	-1.3918700	-1.4931330	2	7.956911	14.197256	0.0023720	0.0293602	40S ribosomal protein S28
P06727	-1.3583680	-0.7667083	-1.0625381	0.5916597	2	8.884167	12.814824	0.0024096	0.0295719	Apolipoprotein A-IV
P02461	-3.5976656	-2.2738894	-2.9357775	1.3237762	2	8.323445	13.522376	0.0024274	0.0295719	Collagen alpha-1(III) chain
Q14314	-1.7692180	-2.0953097	-1.9322639	-0.3260917	2	9.382448	12.231706	0.0024328	0.0295719	Fibroleukin
P09619	-1.6757284	-0.9093138	-1.2925211	0.7664146	2	9.154490	12.419073	0.0024667	0.0298056	Platelet-derived growth factor receptor beta
O15061	-0.4856308	-1.7028211	-1.0942259	-1.2171903	2	9.385413	12.086427	0.0025311	0.0304031	Synemin
P19429	2.0373090	2.1009541	2.0691315	0.0636451	2	7.976624	13.699861	0.0026302	0.0313664	Troponin I, cardiac muscle
P02790	-1.1921329	-1.4568633	-1.3244981	-0.2647304	2	9.385413	11.933537	0.0026422	0.0313664	Hemopexin
P01034	-1.6893296	-1.2428420	-1.4660858	0.4464875	2	8.837162	12.445434	0.0026903	0.0317523	Cystatin-C
P01699	-4.0259605	0.3400879	-1.8429363	4.3660484	2	6.314916	17.240217	0.0027650	0.0323664	Ig lambda chain V-I region VOR
Q07507	-0.9566123	-1.6741554	-1.3153838	-0.7175431	2	8.160106	13.191734	0.0027743	0.0323664	Dermatopontin
P46063	-1.3869124	-0.2234828	-0.8051976	1.1634296	2	9.154885	11.934461	0.0028156	0.0326607	ATP-dependent DNA helicase Q1
Q9Y2Z0	-1.7579777	1.2068202	-0.2755788	2.9647978	2	9.385413	11.674630	0.0028441	0.0327268	Suppressor of G2 allele of SKP1 homolog
P50479	-1.9052893	-2.3347923	-2.1200408	-0.4295030	2	8.131897	13.113069	0.0028535	0.0327268	PDZ and LIM domain protein 4
Q86VP6	-1.0974174	-1.6122394	-1.3548284	-0.5148220	2	8.542953	12.540888	0.0028725	0.0327590	Cullin-associated NEDD8-dissociated protein 1
P28300	-1.2607685	-1.6978873	-1.4793279	-0.4371188	2	7.649016	13.768131	0.0029194	0.0330790	Protein-lysine 6-oxidase
Q15126	-1.0340183	-0.9865904	-1.0103044	0.0474279	2	9.342811	11.607013	0.0029331	0.0330790	Phosphomevalonate kinase
Q86VU5	1.5740900	1.1899321	1.3820110	-0.3841579	2	9.385413	11.512614	0.0029801	0.0334227	Catechol O-methyltransferase domain-containing protein 1
O43143	-1.0109780	-0.7834921	-0.8972350	0.2274859	2	9.289616	11.574983	0.0030027	0.0334915	Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX15
P82663	-0.7938408	-1.9350886	-1.3644647	-1.1412478	2	9.302714	11.525853	0.0030347	0.0336069	28S ribosomal protein S25, mitochondrial
O43175	-2.0890071	-2.0660744	-2.0775407	0.0229327	2	9.173117	11.629663	0.0030510	0.0336069	D-3-phosphoglycerate dehydrogenase
P26447	-1.8777689	-1.1686882	-1.5232285	0.7090807	2	8.774968	12.025412	0.0030627	0.0336069	Protein S100-A4
P13667	-1.1592112	-1.0499894	-1.1046003	0.1092218	2	9.181460	11.588346	0.0030799	0.0336143	Protein disulfide-isomerase A4
Q04760	0.5615089	2.2161884	1.3888487	1.6546795	2	8.599181	12.147102	0.0031249	0.0338146	Lactoylglutathione lyase
Q96CS3	-1.3291851	-1.0516357	-1.1904104	0.2775494	2	9.119924	11.588823	0.0031316	0.0338146	FAS-associated factor 2
P50552	-1.5231187	-0.3481323	-0.9356255	1.1749865	2	9.074476	11.556793	0.0031996	0.0343659	Vasodilator-stimulated phosphoprotein
O95183	-1.3898689	-1.5291947	-1.4595318	-0.1393258	2	9.371170	11.184431	0.0032924	0.0351768	Vesicle-associated membrane protein 5
Q15582	-2.0883637	-2.4627789	-2.2755713	-0.3744151	2	7.899813	12.560835	0.0035188	0.0370726	Transforming growth factor-beta-induced protein ig-h3
Q6UWS5	0.9342388	1.7762603	1.3552496	0.8420216	2	7.068224	13.945225	0.0035193	0.0370726	Protein PET117 homolog, mitochondrial
P46940	-1.2205560	-1.0146605	-1.1176083	0.2058955	2	9.306592	11.010224	0.0035246	0.0370726	Ras GTPase-activating-like protein IQGAP1
Q96JB2	-1.5453539	-2.4514355	-1.9983947	-0.9060817	2	8.142504	12.081209	0.0036586	0.0381425	Conserved oligomeric Golgi complex subunit 3
Q9H1E5	-1.3888294	-0.6312590	-1.0100442	0.7575704	2	9.385413	10.814657	0.0036639	0.0381425	Thioredoxin-related transmembrane protein 4
P62328	-1.2899569	-1.6678529	-1.4789049	-0.3778960	2	7.220282	13.330964	0.0037678	0.0388339	Thymosin beta-4;Hematopoietic system regulatory peptide
Q08945	-2.0713524	-0.7768868	-1.4241196	1.2944656	2	8.385413	11.678065	0.0037686	0.0388339	FACT complex subunit SSRP1
Q5VIR6-4	-1.7550575	-0.0614140	-0.9082357	1.6936435	2	9.130015	10.919027	0.0037890	0.0388469	Vacuolar protein sorting-associated protein 53 homolog
P15924	1.2742208	0.5869741	0.9305974	-0.6872468	2	9.350459	10.675543	0.0038552	0.0391584	Desmoplakin
P01019	-1.0362862	-1.0127277	-1.0245069	0.0235585	2	9.093510	10.889809	0.0038580	0.0391584	Angiotensinogen;Angiotensin-1;Angiotensin-2;Angiotensin-3;Angiotensin-4;Angiotensin 1-9;Angiotensin 1-7;Angiotensin 1-5;Angiotensin 1-4
P83916	-1.9742521	-1.3616457	-1.6679489	0.6126064	2	6.385413	14.963203	0.0038901	0.0392877	Chromobox protein homolog 1
O95486	-1.5003000	-1.1213028	-1.3108014	0.3789972	2	9.187800	10.736201	0.0039420	0.0396155	Protein transport protein Sec24A
P03950	-2.2142952	-1.3775033	-1.7958993	0.8367919	2	8.216113	11.647751	0.0039967	0.0399668	Angiogenin
Q9NRX4	1.2804301	1.4870941	1.3837621	0.2066640	2	9.339127	10.535987	0.0040345	0.0400138	14 kDa phosphohistidine phosphatase
Q9Y5U8	-3.9888327	-0.8866380	-2.4377353	3.1021947	2	9.327097	10.540498	0.0040408	0.0400138	Mitochondrial pyruvate carrier 1
Q8N5M1	-2.0221430	-0.6423210	-1.3322320	1.3798221	2	8.937206	10.851063	0.0040640	0.0400479	ATP synthase mitochondrial F1 complex assembly factor 2
Q562R1	1.3201209	-1.9616415	-0.3207603	-3.2817624	2	9.266665	10.545352	0.0040950	0.0401588	Beta-actin-like protein 2
P05455	-1.2042291	-0.5305125	-0.8673708	0.6737166	2	9.178555	10.565065	0.0041602	0.0403946	Lupus La protein
O15118	-1.6169068	-2.6334712	-2.1251890	-1.0165644	2	6.385413	14.553122	0.0041844	0.0403946	Niemann-Pick C1 protein
Q04721	1.5310391	0.6944075	1.1127233	-0.8366316	2	9.201253	10.522611	0.0041905	0.0403946	Neurogenic locus notch homolog protein 2;Notch 2 extracellular truncation;Notch 2 intracellular domain
P54577	-1.3097944	-0.7452704	-1.0275324	0.5645241	2	8.964139	10.716040	0.0041986	0.0403946	Tyrosine–tRNA ligase, cytoplasmic;Tyrosine–tRNA ligase, cytoplasmic, N-terminally processed
P00747	-0.7054831	-0.9638979	-0.8346905	-0.2584148	2	9.172800	10.440542	0.0043269	0.0413862	Plasminogen;Plasmin heavy chain A;Activation peptide;Angiostatin;Plasmin heavy chain A, short form;Plasmin light chain B
P02748	-1.3394634	-1.1229428	-1.2312031	0.2165205	2	8.865762	10.685485	0.0043459	0.0413862	Complement component C9;Complement component C9a;Complement component C9b
Q9BXR6	-2.3526616	-0.3476437	-1.3501527	2.0050179	2	9.382448	10.250529	0.0043629	0.0413862	Complement factor H-related protein 5
Q7Z3T8	-1.5768427	-1.2158882	-1.3963655	0.3609544	2	8.413206	11.050965	0.0044277	0.0417033	Zinc finger FYVE domain-containing protein 16
Q9Y287	-1.9187015	-1.3340175	-1.6263595	0.5846840	2	9.385413	10.194354	0.0044376	0.0417033	Integral membrane protein 2B;BRI2, membrane form;BRI2 intracellular domain;BRI2C, soluble form;Bri23 peptide
P01303	-0.6538416	-2.1633002	-1.4085709	-1.5094586	2	8.890312	10.577519	0.0044579	0.0417033	Pro-neuropeptide Y;Neuropeptide Y;C-flanking peptide of NPY
Q8WWQ0	-1.3655434	-1.2188019	-1.2921726	0.1467415	2	9.385413	10.140256	0.0045140	0.0420343	PH-interacting protein
O95445	-2.7585923	-2.3195737	-2.5390830	0.4390186	2	9.052359	10.351660	0.0045797	0.0421706	Apolipoprotein M
P27658	-1.5409469	-1.7449610	-1.6429540	-0.2040141	2	9.385413	10.090334	0.0045860	0.0421706	Collagen alpha-1(VIII) chain;Vastatin
Q9UK22	-1.9689505	-0.9835733	-1.4762619	0.9853772	2	6.372396	14.069977	0.0045960	0.0421706	F-box only protein 2
P80723	-1.6385395	-1.4066562	-1.5225978	0.2318833	2	7.910668	11.448438	0.0046195	0.0421706	Brain acid soluble protein 1
P01611	-0.4068850	-2.2194112	-1.3131481	-1.8125261	2	9.385413	10.058567	0.0046325	0.0421706	Ig kappa chain V-I region Wes
Q9UBV8	-1.1877604	-1.1566251	-1.1721927	0.0311353	2	8.885488	10.413473	0.0046866	0.0424726	Peflin
Q9UKX3	2.0400959	1.3472678	1.6936818	-0.6928281	2	9.208912	10.120583	0.0047349	0.0427193	Myosin-13
Q8TDB6	-1.6113146	-0.2207985	-0.9160565	1.3905161	2	9.153547	10.138005	0.0047718	0.0428622	E3 ubiquitin-protein ligase DTX3L
P07360	-0.3859901	-1.5479619	-0.9669760	-1.1619718	2	8.752393	10.443655	0.0048053	0.0429727	Complement component C8 gamma chain
P08582	-1.6638598	0.4414480	-0.6112059	2.1053079	2	9.299314	9.966955	0.0048656	0.0432000	Melanotransferrin
O60262	-1.5147797	-0.9563725	-1.2355761	0.5584072	2	8.388576	10.731124	0.0048733	0.0432000	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
P52907	-0.6186589	-1.0777393	-0.8481991	-0.4590804	2	9.339311	9.904666	0.0049178	0.0432527	F-actin-capping protein subunit alpha-1
P07384	-1.1069382	-0.6510097	-0.8789740	0.4559285	2	9.333139	9.906524	0.0049219	0.0432527	Calpain-1 catalytic subunit
P00352	-1.1650439	-1.1023149	-1.1336794	0.0627289	2	8.402816	10.653653	0.0049615	0.0434132	Retinal dehydrogenase 1
Q6P1N0	-1.6996040	-1.6333624	-1.6664832	0.0662416	2	6.936107	12.521980	0.0049892	0.0434683	Coiled-coil and C2 domain-containing protein 1A
O75348	-1.8464170	-0.7442245	-1.2953207	1.1021925	2	9.377764	9.811092	0.0050240	0.0434758	V-type proton ATPase subunit G 1
P14555	-4.5949034	-1.7126693	-3.1537863	2.8822341	2	6.867951	12.600143	0.0050329	0.0434758	Phospholipase A2, membrane associated
Q9UKS6	1.4436881	0.5239624	0.9838252	-0.9197256	2	8.943424	10.075794	0.0051177	0.0438921	Protein kinase C and casein kinase substrate in neurons protein 3
Q9BSD7	-0.1234697	2.9508964	1.4137133	3.0743661	2	7.080846	12.162214	0.0051243	0.0438921	Cancer-related nucleoside-triphosphatase
Q9BYN0	-1.2973636	-1.2743737	-1.2858687	0.0229898	2	9.180640	9.864374	0.0051672	0.0440735	Sulfiredoxin-1
P04350	-0.5004642	-2.8380383	-1.6692512	-2.3375741	2	6.967833	12.257034	0.0052259	0.0443875	Tubulin beta-4A chain
Q9BXV9	1.5862723	1.2391702	1.4127212	-0.3471021	2	9.163202	9.797960	0.0052989	0.0448202	Uncharacterized protein C14orf142
Q9UL26	-1.2168882	7.9238349	3.3534734	9.1407231	2	8.784585	10.041159	0.0053777	0.0451937	Ras-related protein Rab-22A
Q96A65	-0.6560056	-1.0764957	-0.8662506	-0.4204901	2	9.382448	9.593458	0.0053876	0.0451937	Exocyst complex component 4
P24311	1.7257653	0.4145062	1.0701358	-1.3112591	2	9.295713	9.617255	0.0054499	0.0454918	Cytochrome c oxidase subunit 7B, mitochondrial
P62745	-1.4954700	-0.9675811	-1.2315256	0.5278889	2	8.788016	9.983785	0.0054680	0.0454918	Rho-related GTP-binding protein RhoB
A5D6W6	-2.3613596	-2.0136134	-2.1874865	0.3477462	2	7.868778	10.815729	0.0055206	0.0457417	Fat storage-inducing transmembrane protein 1
Q8IYI6	-1.0552142	-0.8759545	-0.9655844	0.1792596	2	9.385413	9.452880	0.0056398	0.0465401	Exocyst complex component 8
Q8IYU8	-2.9245934	-3.1789343	-3.0517638	-0.2543409	2	6.385413	12.905411	0.0057115	0.0468485	Calcium uptake protein 2, mitochondrial
Q6IC98	-1.1266523	-0.6748287	-0.9007405	0.4518236	2	8.888308	9.747386	0.0057422	0.0468485	GRAM domain-containing protein 4
Q8N142	0.9014180	1.2636791	1.0825486	0.3622611	2	9.201572	9.519259	0.0057464	0.0468485	Adenylosuccinate synthetase isozyme 1
P50991	-1.7861491	-1.1833510	-1.4847501	0.6027981	2	8.685140	9.847405	0.0058465	0.0474077	T-complex protein 1 subunit delta
Q01581	-0.9331228	-2.3288187	-1.6309708	-1.3956959	2	7.186730	11.425555	0.0058617	0.0474077	Hydroxymethylglutaryl-CoA synthase, cytoplasmic
O00625	-1.3732244	-0.9202215	-1.1467230	0.4530029	2	9.385413	9.307306	0.0059204	0.0476208	Pirin
P25311	-1.4767985	-0.6753214	-1.0760599	0.8014770	2	8.673237	9.807893	0.0059350	0.0476208	Zinc-alpha-2-glycoprotein
O75746	-1.5784821	0.3782752	-0.6001034	1.9567573	2	8.893946	9.603894	0.0059996	0.0479394	Calcium-binding mitochondrial carrier protein Aralar1
P62277	-1.5716452	-1.0577672	-1.3147062	0.5138780	2	9.269754	9.331127	0.0060219	0.0479394	40S ribosomal protein S13
Q96GK7	-1.0910279	-1.4460031	-1.2685155	-0.3549752	2	7.917392	10.382537	0.0061228	0.0485522	Fumarylacetoacetate hydrolase domain-containing protein 2A
Q14019	-3.9736692	-0.8629223	-2.4182957	3.1107469	2	6.385413	12.535016	0.0061522	0.0485950	Coactosin-like protein
P61009	-1.0881392	-0.6944647	-0.8913019	0.3936745	2	8.621704	9.660391	0.0062888	0.0494818	Signal peptidase complex subunit 3
P36551	-1.3385428	0.0293104	-0.6546162	1.3678532	2	9.112223	9.290120	0.0063182	0.0495212	Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial
Q96CX2	-0.8346353	-0.9677810	-0.9012081	-0.1331456	2	9.290787	9.153981	0.0063604	0.0496603	BTB/POZ domain-containing protein KCTD12
P19447	-1.4553757	-1.7864940	-1.6209348	-0.3311183	2	7.385413	10.812410	0.0063956	0.0496608	TFIIH basal transcription factor complex helicase XPB subunit
Q9NS69	-1.0286368	-1.1141766	-1.0714067	-0.0855398	2	8.946979	9.359253	0.0064094	0.0496608	Mitochondrial import receptor subunit TOM22 homolog

5.3.3 Confirmation stage

library(stageR)

## 
## Attaching package: 'stageR'

## The following object is masked from 'package:methods':
## 
##     getMethod

pAll <- sapply(
  c("omnibusTest",
    "tissueV",
    "tissueV + locationR:tissueV",
    "tissueV + 0.5 * locationR:tissueV",
    "locationR:tissueV"),
    function(name,assay)
      pull(rowData(assay)[,name],"pval"),
  assay = pe[["proteinRobust"]])
rownames(pAll) <- rownames(pe[["proteinRobust"]])

stageWiseAnalysis <- stageR(pAll[,1], pAll[,-1])
stageWiseAnalysis <- stageWiseAdjustment(stageWiseAnalysis, method = "holm", alpha = 0.05, allowNA = TRUE)

## Removing 1263 features with NA screening hypothesis p-values.

rowData(pe[["proteinRobust"]])$stageWiseAnalysis <- data.frame(pAll)
rowData(pe[["proteinRobust"]])$stageWiseAnalysis[] <- NA
rowData(pe[["proteinRobust"]])$stageWiseAnalysis[getPScreen(stageWiseAnalysis) %>% is.na %>% `!`,] <- getAdjustedPValues(stageWiseAnalysis, onlySignificantGenes=FALSE, order=FALSE)

## The returned adjusted p-values are based on a stage-wise testing approach and are only valid for the provided target OFDR level of 5%. If a different target OFDR level is of interest,the entire adjustment should be re-run.

sigNamesStageWise <- apply(rowData(pe[["proteinRobust"]])$stageWiseAnalysis, 2, function(x) (x < 0.05) %>% which %>% names)

sapply(sigNamesStageWise,length)

##                       omnibusTest                           tissueV 
##                               262                               130 
##       tissueV...locationR.tissueV tissueV...0.5...locationR.tissueV 
##                                95                               221 
##                 locationR.tissueV 
##                                13

for (i in 1:length(sigNamesStageWise))
heatmap(assay(pe[["proteinRobust"]])[sigNamesStageWise[[i]], ], main=names(sigNamesStageWise)[i])

5.4 Confirmation improved

Instead of the Holm correction, we can use a better correction for this specific design in the confirmation stage. If we pass the screening stage we know that at least one null hypothesis related to the contrasts is false. If this is not the case we have made an false positive conclusion, but the multiple testing correction in the screening stage already accounts for that.

In the confirmation stage we have to correct for the maximum number of hypotheses that we can falsely reject. The omnibus hypothesis test essentially tests the overall null hypothesis that the log2 protein abundance is on average equal between atrium and ventriculum both in the left and right heart region. This involves testing simultaneously two model parameters: the main effect for ventriculum and the ventriculum:location interaction. All our hypotheses are based on these two model parameters, so the tests are not independent. The following configurations can occur: - None of the model parameters differ from zero, in which we can falsely reject all hypotheses. However, we already corrected for that in the screening stage! - If only the main ventriculum effect differs from zero, we know that the average log2 fold change between atrium and ventriculum left, right and overall differ from zero. So we falsely reject at most one null hypothesis, i.e. the interaction. - If only interaction differs from zero, only the null hypothesis related to log2 fold change in the left heart region can be falsely rejected. - If both the main effect and the interaction differ from zero it is possible that - the interaction is as large in magnitude as the main effect but opposite in sign. This would mean that the log2 fold change in the right heart region is zero, which we can falsely reject. - the interaction effect is twice as large in magnitude as the main effect but opposite in sign. This would mean that the log2 fold change in left and right side are equal in size but opposite in sign, implying that contrast that averages over the average log2 fold changes left and right would be zeor, which we could falsely reject - all effects are true.

Hence, as soon as we enter the confirmation stage that we can at maximum make one false rejection so for this design and for our hypotheses of interest we do not have to correct for multiple testing in the second stage because we only have to account for the fact that we can at most make one false rejection.

So we can set the method="none"

stageWiseAnalysis <- stageWiseAdjustment(stageWiseAnalysis, method = "none", alpha = 0.05, allowNA = TRUE)

## Removing 1263 features with NA screening hypothesis p-values.

rowData(pe[["proteinRobust"]])$stageWiseAnalysis <- data.frame(pAll)
rowData(pe[["proteinRobust"]])$stageWiseAnalysis[] <- NA
rowData(pe[["proteinRobust"]])$stageWiseAnalysis[getPScreen(stageWiseAnalysis) %>% is.na %>% `!`,] <- getAdjustedPValues(stageWiseAnalysis, onlySignificantGenes=FALSE, order=FALSE)

## The returned adjusted p-values are based on a stage-wise testing approach and are only valid for the provided target OFDR level of 5%. If a different target OFDR level is of interest,the entire adjustment should be re-run.

sigNamesStageWise <- apply(rowData(pe[["proteinRobust"]])$stageWiseAnalysis, 2, function(x) (x < 0.05) %>% which %>% names)

sapply(sigNamesStageWise,length)

##                       omnibusTest                           tissueV 
##                               262                               183 
##       tissueV...locationR.tissueV tissueV...0.5...locationR.tissueV 
##                               145                               248 
##                 locationR.tissueV 
##                                18

for (i in 1:length(sigNamesStageWise))
heatmap(assay(pe[["proteinRobust"]])[sigNamesStageWise[[i]], ], main=names(sigNamesStageWise)[i])

Note, that - our more relaxed FDR correction enables us to reject more null hypotheses in the second stage. - we can recover 18 proteins with significant interactions.

It is also very important to realise that setting the method to correct for multiple testing in the second stage at method = none is only correct for very specific designs and research hypotheses that are assessed. For most analyses we suggest to use the Holm method, which always we provide correct results.