S1 Gene ontology (GO) analysis of the network alignment results
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1 1 Supplementary Material for Effective comparative analysis of protein-protein interaction networks by measuring the steady-state network flow using a Markov model Hyundoo Jeong 1, Xiaoning Qian 1 and Byung-Jun Yoon 1,2 1 Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA. 2 College of Science, Engineering, and Technology, Hamad Bin Khalifa University (HBKU), Doha, Qatar. byoon@qf.org.qa S1 Gene ontology (GO) analysis of the network alignment results Since GO (gene ontology) can be described as a graph and it has a hierarchical structure, all GO terms belong to one of root GO terms: molecular function (MF, GO:3674), biological process (BP, GO:815), and cellular component (CC, GO:5575). Figure S1 shows the number of three root GO terms that commonly appeared in the aligned protein pairs. Note that, in this analysis, we only used GO terms with the IC (information contents) greater than or equal to 2. As we can see, although the percentage of identified root GO terms are not much different to each method, can identify relatively larger number of common GO terms than other competing methods.
2 Yeast - Fly (a) Yeast - Worm (b) Yeast - Human (c) Yeast - Mouse (d) Fly - Worm (e) Fly - Human (f) Figure S1. Number of root GO terms in the alignment results. Number in the bar graph is the percentage of the particular root GO terms.
3 Fly - Mouse (g) Worm - Mouse (h) Worm - Human (i) Human - Mouse (j) Figure S1. Number of root GO terms in the alignment results. Number in the bar graph is the percentage of the particular root GO terms.
4 4 S2 List of GO terms that frequently appear in the network alignment results This section provides the most frequently appearing GO terms in the alignment results. Note that we only consider the commonly identified GO terms in the alignment of, and each table includes the GO terms that commonly appeared more than 1 times. In this analysis, we only used GO terms with the IC (information contents) greater than or equal to 2. Table 1. Frequent GO terms found in Yeast-Fly alignment GO:6468 protein phosphorylation biological process 29 GO:5886 plasma membrane cellular component 27 GO:3735 structural constituent of ribosome molecular function 25 GO:3924 GTPase activity molecular function 12 GO:573 nucleolus cellular component 12 GO:43161 proteasome-mediated ubiquitin-dependent protein catabolic process biological process 12 GO:16573 histone acetylation biological process 1 GO:43565 sequence-specific DNA binding molecular function 1 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 1 Table 2. Frequent GO terms found in Yeast-Worm alignment GO:6468 protein phosphorylation biological process 25 GO:4672 protein kinase activity molecular function 12 GO:5886 plasma membrane cellular component 11
5 5 Table 3. Frequent GO terms found in Yeast-Human alignment GO:573 nucleolus cellular component 85 GO:5886 plasma membrane cellular component 56 GO:6468 protein phosphorylation biological process 49 GO:5783 endoplasmic reticulum cellular component 38 GO:4674 protein serine/threonine kinase activity molecular function 28 GO:22625 cytosolic large ribosomal subunit cellular component 27 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 27 GO:5829 cytosol cellular component 26 GO:4672 protein kinase activity molecular function 21 GO:4842 ubiquitin-protein transferase activity molecular function 2 GO:6366 transcription from RNA polymerase II promoter biological process 2 GO:3924 GTPase activity molecular function 16 GO:43565 sequence-specific DNA binding molecular function 13 GO:3743 translation initiation factor activity molecular function 12 GO:4843 thiol-dependent ubiquitin-specific protease activity molecular function 12 GO:5665 DNA-directed RNA polymerase II, core complex cellular component 12 GO:568 anaphase-promoting complex cellular component 12 GO:5794 Golgi apparatus cellular component 12 GO:16887 ATPase activity molecular function 12 GO:22627 cytosolic small ribosomal subunit cellular component 12 GO:596 GTPase activator activity molecular function 11 GO:5669 transcription factor TFIID complex cellular component 11 GO:5768 endosome cellular component 1 Table 4. Frequent GO terms found in Yeast-Mouse alignment GO:6468 protein phosphorylation biological process 38 GO:5886 plasma membrane cellular component 28 GO:4672 protein kinase activity molecular function 22 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 2 GO:573 nucleolus cellular component 18 GO:5743 mitochondrial inner membrane cellular component 17 GO:4674 protein serine/threonine kinase activity molecular function 14 GO:43565 sequence-specific DNA binding molecular function 14 GO:5783 endoplasmic reticulum cellular component 12 Table 5. Frequent GO terms found in Fly-Worm alignment GO:5739 mitochondrion cellular component 26 GO:5886 plasma membrane cellular component 23 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 22 GO:834 determination of adult lifespan biological process 12 GO:5938 cell cortex cellular component 11 GO:43565 sequence-specific DNA binding molecular function 11
6 6 Table 6. Frequent GO terms found in Fly-Human alignment GO:5739 mitochondrion cellular component 74 GO:5886 plasma membrane cellular component 59 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 47 GO:7113 catalytic step 2 spliceosome cellular component 41 GO:5794 Golgi apparatus cellular component 3 GO:5783 endoplasmic reticulum cellular component 27 GO:5654 nucleoplasm cellular component 25 GO:52 proteasome complex cellular component 23 GO:5615 extracellular space cellular component 22 GO:573 nucleolus cellular component 21 GO:122 negative regulation of transcription from RNA polymerase II promoter biological process 19 GO:6468 protein phosphorylation biological process 16 GO:8134 transcription factor binding molecular function 16 GO:3677 DNA binding molecular function 15 GO:4674 protein serine/threonine kinase activity molecular function 15 GO:5813 centrosome cellular component 15 GO:43565 sequence-specific DNA binding molecular function 15 GO:16592 mediator complex cellular component 13 GO:776 kinetochore cellular component 12 GO:35267 NuA4 histone acetyltransferase complex cellular component 12 GO:45893 positive regulation of transcription, DNA-templated biological process 12 GO:5829 cytosol cellular component 11 GO:5925 focal adhesion cellular component 11 GO:5669 transcription factor TFIID complex cellular component 1 GO:16567 protein ubiquitination biological process 1 Table 7. Frequent GO terms found in Fly-Mouse alignment GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 55 GO:5886 plasma membrane cellular component 5 GO:122 negative regulation of transcription from RNA polymerase II promoter biological process 29 GO:3677 DNA binding molecular function 26 GO:6468 protein phosphorylation biological process 24 GO:43565 sequence-specific DNA binding molecular function 2 GO:4674 protein serine/threonine kinase activity molecular function 16 GO:5794 Golgi apparatus cellular component 15 GO:16592 mediator complex cellular component 15 GO:7411 axon guidance biological process 13 GO:45893 positive regulation of transcription, DNA-templated biological process 13 GO:37 transcription factor activity, sequence-specific DNA binding molecular function 12 GO:5829 cytosol cellular component 12 GO:177 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding molecular function 11 GO:5783 endoplasmic reticulum cellular component 11 GO:6355 regulation of transcription, DNA-templated biological process 11 GO:42384 cilium assembly biological process 11 GO:45892 negative regulation of transcription, DNA-templated biological process 11 Table 8. Frequent GO terms found in Worm-Mouse alignment GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 43 GO:5886 plasma membrane cellular component 22 GO:6468 protein phosphorylation biological process 17 GO:122 negative regulation of transcription from RNA polymerase II promoter biological process 14 GO:4674 protein serine/threonine kinase activity molecular function 1 GO:5783 endoplasmic reticulum cellular component 1
7 7 Table 9. Frequent GO terms found in Worm-Human alignment GO:5739 mitochondrion cellular component 51 GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 39 GO:5886 plasma membrane cellular component 3 GO:4674 protein serine/threonine kinase activity molecular function 16 GO:122 negative regulation of transcription from RNA polymerase II promoter biological process 15 GO:5813 centrosome cellular component 13 GO:6468 protein phosphorylation biological process 13 GO:5654 nucleoplasm cellular component 11 GO:5783 endoplasmic reticulum cellular component 11 GO:43565 sequence-specific DNA binding molecular function 11 GO:5829 cytosol cellular component 1 GO:162 membrane cellular component 1
8 8 Table 1. Frequent GO terms found in Human-Mouse alignment GO:45944 positive regulation of transcription from RNA polymerase II promoter biological process 184 GO:5886 plasma membrane cellular component 181 GO:45893 positive regulation of transcription, DNA-templated biological process 93 GO:5615 extracellular space cellular component 92 GO:122 negative regulation of transcription from RNA polymerase II promoter biological process 88 GO:37 transcription factor activity, sequence-specific DNA binding molecular function 66 GO:3677 DNA binding molecular function 6 GO:6468 protein phosphorylation biological process 58 GO:45892 negative regulation of transcription, DNA-templated biological process 56 GO:5783 endoplasmic reticulum cellular component 54 GO:4674 protein serine/threonine kinase activity molecular function 52 GO:5829 cytosol cellular component 52 GO:162 membrane cellular component 51 GO:5794 Golgi apparatus cellular component 41 GO:573 nucleolus cellular component 4 GO:8284 positive regulation of cell proliferation biological process 4 GO:9986 cell surface cellular component 37 GO:4366 negative regulation of apoptotic process biological process 37 GO:5813 centrosome cellular component 32 GO:8134 transcription factor binding molecular function 28 GO:4283 protein homodimerization activity molecular function 27 GO:43565 sequence-specific DNA binding molecular function 27 GO:3112 extracellular matrix cellular component 26 GO:1628 positive regulation of gene expression biological process 25 GO:3713 transcription coactivator activity molecular function 24 GO:8285 negative regulation of cell proliferation biological process 24 GO:44212 transcription regulatory region DNA binding molecular function 24 GO:5925 focal adhesion cellular component 23 GO:16324 apical plasma membrane cellular component 23 GO:19899 enzyme binding molecular function 22 GO:5524 ATP binding molecular function 21 GO:46982 protein heterodimerization activity molecular function 21 GO:35556 intracellular signal transduction biological process 2 GO:5654 nucleoplasm cellular component 19 GO:5764 lysosome cellular component 19 GO:46777 protein autophosphorylation biological process 19 GO:7 canonical Wnt signaling pathway biological process 19 GO:3682 chromatin binding molecular function 17 GO:3714 transcription corepressor activity molecular function 17 GO:5814 centriole cellular component 17 GO:9897 external side of plasma membrane cellular component 17 GO:48471 perinuclear region of cytoplasm cellular component 17 GO:4672 protein kinase activity molecular function 16 GO:5887 integral component of plasma membrane cellular component 16 GO:1991 protein kinase binding molecular function 16 GO:4282 identical protein binding molecular function 16 GO:99 negative regulation of canonical Wnt signaling pathway biological process 16 GO:79 nuclear chromatin cellular component 15 GO:5777 peroxisome cellular component 15 GO:658 proteolysis biological process 15 GO:1818 peptidyl-tyrosine phosphorylation biological process 15 GO:177 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding molecular function 14 GO:4713 protein tyrosine kinase activity molecular function 14 GO:5923 bicellular tight junction cellular component 14 GO:6974 cellular response to DNA damage stimulus biological process 14 GO:7179 transforming growth factor beta receptor signaling pathway biological process 14 GO:765 sensory perception of sound biological process 14 GO:16592 mediator complex cellular component 14 GO:7374 positive regulation of ERK1 and ERK2 cascade biological process 14 GO:287 magnesium ion binding molecular function 13 GO:559 calcium ion binding molecular function 13 GO:6355 regulation of transcription, DNA-templated biological process 13 GO:359 BMP signaling pathway biological process 13 GO:4587 innate immune response biological process 13 GO:784 nuclear chromosome, telomeric region cellular component 12 GO:3743 translation initiation factor activity molecular function 12 GO:512 receptor binding molecular function 12 GO:564 basement membrane cellular component 12 GO:647 protein dephosphorylation biological process 12 GO:876 voltage-gated potassium channel complex cellular component 12 GO:16323 basolateral plasma membrane cellular component 12 GO:43123 positive regulation of I-kappaB kinase/nf-kappab signaling biological process 12 GO:5192 positive regulation of NF-kappaB transcription factor activity biological process 12 GO:5667 transcription factor complex cellular component 11 GO:5929 cilium cellular component 11 GO:813 beta-catenin binding molecular function 11 GO:327 lamellipodium cellular component 11 GO:34976 response to endoplasmic reticulum stress biological process 11 GO:3664 ciliary basal body cellular component 11 GO:4365 positive regulation of apoptotic process biological process 11 GO:5821 protein stabilization biological process 11 GO:7185 potassium ion transmembrane transport biological process 11
Biological Process Term Enrichment
Biological Process Term Enrichment cellular protein localization cellular macromolecule localization intracellular protein transport intracellular transport generation of precursor metabolites and energy
GO ID GO term Number of members GO: translation 225 GO: nucleosome 50 GO: calcium ion binding 76 GO: structural
GO ID GO term Number of members GO:0006412 translation 225 GO:0000786 nucleosome 50 GO:0005509 calcium ion binding 76 GO:0003735 structural constituent of ribosome 170 GO:0019861 flagellum 23 GO:0005840
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Supplementary Information 16 Cellular Component % of Genes 50 45 40 35 30 25 20 15 10 5 0 human mouse extracellular other membranes plasma membrane cytosol cytoskeleton mitochondrion ER/Golgi translational
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