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Novel Factors In The Pathogenesis Of Psoriasis And Potential Drug Candidates Are Found With Systems Biology Approach

M. Manczinger, L. Kemény
Published 2013 · Biology, Medicine

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Psoriasis is a multifactorial inflammatory skin disease characterized by increased proliferation of keratinocytes, activation of immune cells and susceptibility to metabolic syndrome. Systems biology approach makes it possible to reveal novel important factors in the pathogenesis of the disease. Protein-protein, protein-DNA, merged (containing both protein-protein and protein-DNA interactions) and chemical-protein interaction networks were constructed consisting of differentially expressed genes (DEG) between lesional and non-lesional skin samples of psoriatic patients and/or the encoded proteins. DEGs were determined by microarray meta-analysis using MetaOMICS package. We used STRING for protein-protein, CisRED for protein-DNA and STITCH for chemical-protein interaction network construction. General network-, cluster- and motif-analysis were carried out in each network. Many DEG-coded proteins (CCNA2, FYN, PIK3R1, CTGF, F3) and transcription factors (AR, TFDP1, MEF2A, MECOM) were identified as central nodes, suggesting their potential role in psoriasis pathogenesis. CCNA2, TFDP1 and MECOM might play role in the hyperproliferation of keratinocytes, whereas FYN may be involved in the disturbed immunity in psoriasis. AR can be an important link between inflammation and insulin resistance, while MEF2A has role in insulin signaling. A controller sub-network was constructed from interlinked positive feedback loops that with the capability to maintain psoriatic lesional phenotype. Analysis of chemical-protein interaction networks detected 34 drugs with previously confirmed disease-modifying effects, 23 drugs with some experimental evidences, and 21 drugs with case reports suggesting their positive or negative effects. In addition, 99 unpublished drug candidates were also found, that might serve future treatments for psoriasis.
This paper references
10.1186/1471-2164-7-108
Network motifs: structure does not determine function
P. Ingram (2005)
10.1016/S0140-6736(07)61128-3
Pathogenesis and clinical features of psoriasis
C. Griffiths (2007)
10.1371/journal.pone.0030308
Post-Therapeutic Relapse of Psoriasis after CD11a Blockade Is Associated with T Cells and Inflammatory Myeloid DCs
L. Johnson-Huang (2012)
10.1049/iet-syb:20070036
Proximity of intracellular regulatory networks to monotone systems.
Avi Ma’ayan (2008)
10.1016/j.ajpath.2012.07.008
Androgen receptor influences on body defense system via modulation of innate and adaptive immune systems: lessons from conditional AR knockout mice.
Jiann-jyh Lai (2012)
10.1038/jid.2010.103
Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions.
B. Davidovici (2010)
10.2337/db12-0920
Fyn Deficiency Promotes a Preferential Increase in Subcutaneous Adipose Tissue Mass and Decreased Visceral Adipose Tissue Inflammation
Ting-Wen A. Lee (2013)
10.1093/bioinformatics/btn647
arrayQualityMetrics—a bioconductor package for quality assessment of microarray data
A. Kauffmann (2009)
10.1074/jbc.M111.313809
Absence of a Human DnaJ Protein hTid-1S Correlates with Aberrant Actin Cytoskeleton Organization in Lesional Psoriatic Skin*
Ji Hye Choi (2012)
10.1371/journal.pone.0044274
Meta-Analysis Derived (MAD) Transcriptome of Psoriasis Defines the “Core” Pathogenesis of Disease
S. Tian (2012)
10.1016/0190-9622(95)91487-0
Exacerbation and induction of psoriasis by angiotensin-converting enzyme inhibitors.
K. Ikai (1995)
10.1016/j.jaad.2012.08.015
Psoriasis and metabolic syndrome: a systematic review and meta-analysis of observational studies.
A. Armstrong (2013)
10.1016/j.genhosppsych.2009.08.008
Onset of psoriasis during therapy with fluoxetine.
Lynnette Tan Pei Lin (2010)
10.1684/ejd.2008.0403
Investigation for the leptin 1 and LEP G2548A gene polymorphism in psoriasis.
N. Senturk (2008)
10.1592/phco.31.11.1045
Atorvastatin for the Treatment of Plaque‐Type Psoriasis
T. Faghihi (2011)
10.1002/jcp.22872
Lithium Regulates Keratinocyte Proliferation Via Glycogen Synthase Kinase 3 and NFAT2 (Nuclear Factor of Activated T Cells 2)
P. Hampton (2012)
10.1016/j.clindermatol.2007.10.023
Nonstandard and off-label therapies for psoriasis.
Caroline P. Halverstam (2008)
10.1093/BIOINFORMATICS/BTM032
NetMatch: a Cytoscape plugin for searching biological networks
A. Ferro (2007)
10.1038/SJ.JID.5700943
PPARδ Enhances Keratinocyte Proliferation in Psoriasis and Induces Heparin-Binding EGF-Like Growth Factor
M. Romanowska (2008)
Psoriasis during therapy with olanzapine.
A. Latini (2003)
10.1126/SCIENCE.1113834
Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions
Onn Brandman (2005)
10.1016/J.JAAD.2007.05.040
Efficacy of simvastatin in plaque psoriasis: A pilot study.
I. Shirinsky (2007)
10.1046/j.1365-4362.1999.00500.x
The role of salicylic acid in the treatment of psoriasis
M. Lebwohl (1999)
10.1016/j.jaad.2007.12.035
Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial.
S. Kurd (2008)
10.1371/journal.pone.0002737
Type I Interferon: Potential Therapeutic Target for Psoriasis?
Y. Yao (2008)
IFN-gamma and TNF-alpha synergize to inhibit CTGF expression in human lung endothelial cells
R Laug (2012)
10.1093/bioinformatics/bts485
An R package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection
Xingbin Wang (2012)
10.1136/ebmed-2011-100388
Thiazolidinediones for plaque psoriasis: a systematic review and meta-analysis
A. Malhotra (2012)
10.1083/jcb.201102085
A novel function for Cyclin A2: Control of cell invasion via RhoA signaling
N. Arsic (2012)
10.1111/bjd.12049
STAT1 expression and activation is increased in lesional psoriatic skin
A. Hald (2013)
10.1007/s00403-004-0489-9
Complete resolution of psoriasis in a patient treated with stealth liposomal doxorubicin and carboplatin for ovarian cancer
C. Pisano (2004)
10.1093/bioinformatics/btq675
Cytoscape 2.8: new features for data integration and network visualization
Michael E. Smoot (2011)
10.1126/SCIENCE.286.5439.509
Emergence of scaling in random networks
Barabási (1999)
10.1093/nar/gkr1071
MetaQC: objective quality control and inclusion/exclusion criteria for genomic meta-analysis
D. D. Kang (2012)
10.1093/nar/gkr1011
STITCH 3: zooming in on protein–chemical interactions
M. Kuhn (2012)
Psoriasis disappearance after the first phase of an oncologic treatment: a serendipity case report.
R. Cagiano (2008)
10.2174/138920010791526097
Rottlerin: bases for a possible usage in psoriasis.
E. Maioli (2010)
10.1001/ARCHDERM.1980.01640340011006
Treatment of psoriasis with daunorubicin and cytarabine.
D. Kohn (1980)
Br J Dermatol
10.1038/nprot.2007.324
Integration of biological networks and gene expression data using Cytoscape
M. Cline (2007)
10.1096/fasebj.13.3.495
Psoriatic keratinocytes show reduced IRF‐1 and STAT‐1α activation in response to γ‐IFN
M. Jackson (1999)
10.1111/j.1600-065X.2008.00733.x
Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases
B. Beutler (2009)
10.1002/hep.22252
Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor
Hung-Yun Lin (2008)
10.4049/jimmunol.1001426
The IFN-γ–Dependent Suppressor of Cytokine Signaling 1 Promoter Activity Is Positively Regulated by IFN Regulatory Factor-1 and Sp1 but Repressed by Growth Factor Independence-1b and Krüppel-Like Factor-4, and It Is Dysregulated in Psoriatic Keratinocytes
S. Madonna (2010)
10.1002/gepi.21689
Robust and Powerful Tests for Rare Variants Using Fisher's Method to Combine Evidence of Association From Two or More Complementary Tests
A. Derkach (2013)
10.1038/jid.2011.200
The dark side of regulatory T cells in psoriasis.
D. C. Soler (2011)
10.1007/BF00403945
Testosterone serum levels in male psoriatics
W. Schwarz (2004)
10.1073/pnas.0506580102
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian (2005)
10.1001/ARCHDERM.136.5.609
Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation.
C. Ellis (2000)
Network analysis: methodological foundations. Berlin; New York: Springer. xii, 471 p. p. Network Analysis in Psoriasis PLOS ONE | www.plosone.org 13 November
U Brandes (2005)
10.1093/bioinformatics/bti551
BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks
Steven Maere (2005)
10.1080/00015550410024634
Exacerbation of psoriasis after treatment with an EGFR tyrosine kinase inhibitor.
Markella-Pagona Zorzou (2004)
10.1016/j.intimp.2012.04.003
Monocyte-derived interferon-alpha primed dendritic cells in the pathogenesis of psoriasis: new pieces in the puzzle.
A. Farkas (2012)
10.1001/ARCHDERM.1972.01620040088028
Remission of psoriasis vulgaris from the use of nerve-blocking agents.
H. Perlman (1972)
Stat3 as a therapeutic target for the treatment of psoriasis : a clinical feasibility study with STA-21, a Stat3 inhibitor
三好 研 (2010)
10.1111/bjd.12271
Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin
C. Buerger (2013)
10.4049/jimmunol.176.3.1431
Protein Expression of TNF-α in Psoriatic Skin Is Regulated at a Posttranscriptional Level by MAPK-Activated Protein Kinase 21
C. Johansen (2006)
10.1111/j.1365-4362.1990.tb03753.x
Psoriasis Without Neutrophils
D. Paslin (1990)
10.1016/S0140-6736(07)61129-5
Current and future management of psoriasis
A. Menter (2007)
10.1016/0020-7101(95)01135-2
A new drug classification for computer systems: the ATC extension code.
G. Miller (1995)
10.1093/nar/gkq973
The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored
Damian Szklarczyk (2011)
10.1038/jid.2012.123
Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis.
C. Buerger (2012)
10.1159/000018281
Dystrophic Psoriatic Fingernails Treated with 1% 5-Fluorouracil in a Nail Penetration-Enhancing Vehicle: A Double-Blind Study
E. D. de Jong (1999)
10.1080/09546630510011801
Evaluation of the efficacy of topical caffeine in the treatment of psoriasis vulgaris
A. Vali (2005)
10.1097/01.mjt.0000174350.82270.da
A Report on Three Recent Clinical Trials Using Mahonia aquifolium 10% Topical Cream and a Review of the Worldwide Clinical Experience With Mahonia aquifolium for the Treatment of Plaque Psoriasis
W. Gulliver (2005)
Network Analysis in Psoriasis PLOS ONE | www.plosone
10.1093/nar/gkj075
cisRED: a database system for genome-scale computational discovery of regulatory elements
G. Robertson (2006)
10.1080/09546630510043202
Efficacy of 2 weeks' application of theophylline ointment in psoriasis vulgaris
E. Papakostantinou (2005)
10.1186/1756-0500-3-277
EMA - A R package for Easy Microarray data analysis
N. Servant (2010)
10.1016/J.BBALIP.2007.02.004
Peroxisome proliferator-activated receptors (PPARs) in skin health, repair and disease.
L. Michalik (2007)
10.1111/j.1365-2141.2012.09078.x
BCR‐ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia
S. Roy (2012)
10.1080/000155501317140061
Calcium channel blockers intake and psoriasis: a case-control study.
A. Cohen (2001)
10.1111/j.1600-0625.1998.tb00307.x
Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems
T. Scholzen (1998)
10.1046/J.0022-202X.2001.01537.X
Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation.
S. Kippenberger (2001)
PPARdelta enhances keratinocyte proliferation in psoriasis and induces heparin-binding EGF-like growth factor.
M. Romanowska (2008)
10.2337/db11-1433
Attenuated Pik3r1 Expression Prevents Insulin Resistance and Adipose Tissue Macrophage Accumulation in Diet-Induced Obese Mice
C. McCurdy (2012)
10.1111/j.1346-8138.2007.00369.x
Exacerbation of psoriasis in a chronic myelogenous leukemia patient treated with imatinib
S. M. Woo (2007)
10.1038/msb4100138
Hubs in biological interaction networks exhibit low changes in expression in experimental asthma
Xin Lu (2007)
Can nicotine use alleviate symptoms of psoriasis?
J. Staples (2012)
10.1111/j.1600-0625.2011.01343.x
Statins inhibit chemotactic interaction between CCL20 and CCR6 in vitro: possible relevance to psoriasis treatment
T. Kim (2011)
10.1016/j.bcp.2008.12.021
Fyn kinase is a direct molecular target of delphinidin for the inhibition of cyclooxygenase-2 expression induced by tumor necrosis factor-alpha.
M. K. Hwang (2009)
10.1111/j.1365-2125.2012.04221.x
Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases.
Rui Han (2012)
10.3109/09546634.2012.672706
Intralesional therapy for psoriasis
T. Wang (2013)
10.1038/labinvest.2010.208
Interferon-γ-induced increases in intestinal epithelial macromolecular permeability requires the Src kinase Fyn
D. Smyth (2011)
10.1038/emboj.2012.181
Dual functions of DP1 promote biphasic Wnt‐on and Wnt‐off states during anteroposterior neural patterning
Wan-Tae Kim (2012)
10.4049/jimmunol.0802999
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis1
L. van der Fits (2009)
10.1371/journal.pone.0050093
NetMODE: Network Motif Detection without Nauty
X. Li (2012)
Insulin-like growth factor II induces interleukin-6 expression via NFkappaB activation in psoriasis.
Y. Kwon (2000)
10.1016/j.jdermsci.2012.11.002
NF-κB: an essential transcription factor in psoriasis.
A. Goldminz (2013)
10.1016/B978-1-898563-96-9.50010-5
5 – Pathogenesis of disease
J. C. Lee (2004)
10.1159/000247215
Chloroquine stimulates the mitogen-driven lymphocyte proliferation in patients with psoriasis.
R. Schopf (1993)
10.1093/nar/gkj102
From genomics to chemical genomics: new developments in KEGG
M. Kanehisa (2006)
10.1093/nar/gkh012
JASPAR: an open-access database for eukaryotic transcription factor binding profiles
A. Sandelin (2004)
10.1038/jid.2012.339
Global epidemiology of psoriasis: a systematic review of incidence and prevalence.
R. Parisi (2013)
NF-kappaB: An essential transcription factor in psoriasis
AM Goldminz (2013)
10.1016/j.cities.2012.03.001
Power laws, Pareto distributions and Zipf's law
M. Newman (2004)
10.1016/j.ejps.2013.02.009
Antiproliferative effect of two novel COX-2 inhibitors on human keratinocytes.
C. Sticozzi (2013)
10.1016/j.ajhg.2012.03.012
PSORS2 is due to mutations in CARD14.
C. Jordan (2012)
10.1371/journal.pone.0045430
IFN-γ and TNF-α Synergize to Inhibit CTGF Expression in Human Lung Endothelial Cells
Roderich Laug (2012)
2013) mTOR and its downstream signalling components are activated in psoriatic skin
C Buerger
BCRABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia
S Roy (2012)
Network Analysis: Methodological Foundations
Chris Arney (2012)
10.1186/1471-2105-11-S9-S6
Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants
Alexander A. Morgan (2010)
10.1159/000248839
Generalized pustular psoriasis precipitated by diclofenac and indomethacin.
E. Sendagorta (1987)
10.1016/j.jaad.2007.11.023
Association between use of thiazolidinediones or other oral antidiabetics and psoriasis: A population based case-control study.
Y. Brauchli (2008)
10.1097/MJT.0b013e3181c6c0c2
Psoriasis induced by losartan therapy: a case report and review of the literature.
G. Lamba (2011)
10.1124/jpet.107.134080
Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis
W. Tse (2008)
10.1038/jid.2008.122
Reactive oxygen species in tumor necrosis factor-alpha-activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease.
Chen N. Young (2008)
10.1093/nar/24.1.238
TRANSFAC: a database on transcription factors and their DNA binding sites
E. Wingender (1996)
10.1159/000345762
Complete Resolution of Erythrodermic Psoriasis in an HIV and HCV Patient Unresponsive to Antipsoriatic Treatments after Highly Active Antiretroviral Therapy (Ritonavir, Atazanavir, Emtricitabine, Tenofovir)
A. Chiricozzi (2012)
10.1186/1471-2105-11-408
Comparison study of microarray meta-analysis methods
A. Campain (2010)
10.1074/jbc.M910259199
The MEF2A Isoform Is Required for Striated Muscle-specific Expression of the Insulin-responsive GLUT4 Glucose Transporter*
S. Mora (2000)
mTOR and its downstream signalling components are activated in psoriatic skin
C Buerger (2013)
Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
L. Tsoi (2012)
10.1016/J.CLIM.2004.09.001
The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules.
A. Johnston (2005)
10.1038/jid.2012.184
Expanding the Psoriasis Disease Profile: Interrogation of the Skin and Serum of Patients with Moderate-to-Severe Psoriasis
M. Suárez-Fariñas (2012)
10.1046/J.1523-1747.1999.00639.X
Rolipram inhibits staphylococcal enterotoxin B-mediated induction of the human skin-homing receptor on T lymphocytes.
L. Santamaria (1999)
10.3109/09546630903496975
Rifampicin – A mild immunosuppressive agent for psoriasis
N. Tsankov (2011)
10.1038/SJ.JID.5700488
Increased expression of Wnt5a in psoriatic plaques.
J. Reischl (2007)
10.1038/nmeth.1938
Detecting overlapping protein complexes in protein-protein interaction networks
Tamás Nepusz (2012)
Psoriatic keratinocytes show reduced IRF-1 and STAT-1alpha activation in response to gamma-IFN.
M. Jackson (1999)
10.1006/BBRC.2000.3806
Insulin-like Growth Factor II Induces Interleukin-6 Expression via NFκB Activation in Psoriasis
Y. Kwon (2000)
10.1038/jid.2009.173
Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin.
J. Gudjonsson (2009)
10.1016/J.JAAD.2003.09.018
Micellar paclitaxel improves severe psoriasis in a prospective phase II pilot study.
Alison Ehrlich (2004)
10.1067/MAI.2001.114707
Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines.
M. L. Giustizieri (2001)
10.1111/j.1365-2230.2008.03026.x
Serum levels of transforming growth factor‐β1 in patients with mild psoriasis vulgaris and effect of treatment with biological drugs
P. G. Kallimanis (2009)



This paper is referenced by
10.18699/vj18.378
RNAI-MEDIATED SILENCING OF MATRIX METALLOPROTEINASE 1 IN EPIDERMAL KERATINOCYTES INFLUENCES THE BIOLOGICAL EFFECTS OF INTERLEUKIN 17A
Julia Mogulevtseva (2018)
10.1038/s41419-019-2212-y
Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation
Sowjanya Thatikonda (2020)
AN INTEGRATED NETWORK ANALYSIS OF PSORIASIS: A NOVEL APPROACH TO DISEASE PATHOLOGY
Alex Anand (2015)
Investigating the role of epigenetics in the regulation of inflammatory skin disease
K. Wu (2016)
Aplicación de métodos de aprendizaje automático para el estudio de la comorbilidad inversa entre cáncer y trastornos del sistema nervioso central
Kristina Ibáñez Garikano (2015)
10.1016/S1875-5364(15)30075-3
Drug-target networks for Tanshinone IIA identified by data mining.
Sibao Chen (2015)
10.14232/phd.2857
High Throughput Screening of Gene Expression for the Investigation of Multifactorial Dermatological Disorders
M. Máté (2016)
10.3390/ijms21030699
Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis
Julius Schwingen (2020)
A Computational approach for identifying novel micro RNAs from Genome Wide Association Studies of Psoriasis
Harishchander Anandaram (2014)
10.1134/S1022795418080094
Impact of Metalloproteinase 1 Deficiency Induced by Specific Small Hairpin RNA on the Physiological Effects of Tumor Necrosis Factor
J. Mogulevtseva (2018)
10.1093/bioinformatics/btu799
Graphical algorithm for integration of genetic and biological data: proof of principle using psoriasis as a model
L. Tsoi (2015)
10.3390/genes11080914
Using Micro- and Macro-Level Network Metrics Unveils Top Communicative Gene Modules in Psoriasis
Reyhaneh Naderi (2020)
Network analysis of Urocortins.
Shao-jun Chen (2016)
COMPUTATIONAL APPROACH FOR IDENTIFYING THERAPEUTIC MICRO RNAs
D. A. Anand (2014)
10.2147/BTT.S188286
Therapeutic drug monitoring of biologics in psoriasis
M. M. Liau (2019)
10.1007/s11010-017-3090-1
Splicing factors differentially expressed in psoriasis alter mRNA maturation of disease-associated EDA+ fibronectin
E. Szlavicz (2017)
10.5314/WJD.V3.I3.50
What have we learned about non-involved psoriatic skin from large-scale gene expression studies?
E. Szlavicz (2014)
BINDING SITE ANALYSIS OF MICRORNAS TARGET INTERACTION FROM GENOME WIDE ASSOCIATION STUDIES
D. A. Anand (2014)
10.1016/j.jid.2019.07.691
First glimpse of epigenetic effects on pemphigus foliaceus.
M. Spadoni (2019)
10.3390/cancers12092416
Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
Thayne Woycinck Kowalski (2020)
10.14232/phd.4101
Investigations on mRNA maturation disturbancies in the pathogenesis of psoriasis
Szlávicz Eszter (2017)
10.1097/MIB.0000000000001150
Colonic Phenotypes Are Associated with Poorer Response to Anti-TNF Therapies in Patients with IBD
S. Yoon (2017)
10.1111/ced.13024
Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis‐surrogate keratinocytes and skin substitutes
S. Ma (2017)
10.1002/cpt.769
Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
M. Manczinger (2018)
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