Skip to main content
Erschienen in: Immunologic Research 5/2021

23.07.2021 | Original Article

A graph centrality-based approach for candidate gene prediction for type 1 diabetes

verfasst von: N. B. Thummadi, E. Vishnu, E. V. Subbiah, P. Manimaran

Erschienen in: Immunologic Research | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

Abstract

Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes is an autoimmune disease that may pose life-threatening situations to individuals. In most cases, cytotoxic T lymphocytes (CTLs) promotes killing of islets of Langerhans in the pancreas, which harbour insulin-producing beta cells. The trigger for autoimmune attack is still unclear; therefore, identifying and targeting candidate genes are imperative to hinder its deleterious effects. In the present study, we focused on identification of new candidate genes for T1DM. For our study, we exclusively selected immune-related genes as they play a crucial role in T1DM. We constructed and analysed a human immunome signalling network (directed network) to identify the new candidate genes through various graph centrality measures combining with Gene Ontology (GO). As a result, we identified 4 new candidate genes which may act as potential drug targets for T1DM. We further validated for their disease relevance through literature survey and pathway analysis and found that 3 out of 4 predicted genes mirrored their well-established roles as potential targets for T1DM.
Literatur
1.
2.
Zurück zum Zitat Allen HF, Klingensmith GJ, Jensen P, Simoes E, Hayward A, Chase HP. Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes A randomized clinical study. Diabetes Care. 1999;22:1703–7.CrossRefPubMed Allen HF, Klingensmith GJ, Jensen P, Simoes E, Hayward A, Chase HP. Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes A randomized clinical study. Diabetes Care. 1999;22:1703–7.CrossRefPubMed
4.
Zurück zum Zitat Tranchevent LC, Capdevila FB, Nitsch D, De Moor B, De Causmaecker P, et al. A guide to web tools to prioritize candidate genes. Brief Bioinform. 2010;12:22–32.CrossRefPubMed Tranchevent LC, Capdevila FB, Nitsch D, De Moor B, De Causmaecker P, et al. A guide to web tools to prioritize candidate genes. Brief Bioinform. 2010;12:22–32.CrossRefPubMed
5.
Zurück zum Zitat Rao SB, Priyanka PL, Manimaran P. Candidate gene identification for systemic lupus erythematosus using network centrality measures and gene ontology. PLoS One. 2013;8:e81766.CrossRef Rao SB, Priyanka PL, Manimaran P. Candidate gene identification for systemic lupus erythematosus using network centrality measures and gene ontology. PLoS One. 2013;8:e81766.CrossRef
6.
Zurück zum Zitat Yana B. Disease gene prioritization. PLoS Comput Biol. 2013;9:e1002902.CrossRef Yana B. Disease gene prioritization. PLoS Comput Biol. 2013;9:e1002902.CrossRef
7.
Zurück zum Zitat Richard AG, Jason YL, Lina LF, Robert JBR, Diane F, Merridee AW. Analysis of protein sequence and interaction data for candidate disease gene prediction. Nucleic Acids Res. 2006;34:e130.CrossRef Richard AG, Jason YL, Lina LF, Robert JBR, Diane F, Merridee AW. Analysis of protein sequence and interaction data for candidate disease gene prediction. Nucleic Acids Res. 2006;34:e130.CrossRef
8.
Zurück zum Zitat Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445:881–5.CrossRefPubMed Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445:881–5.CrossRefPubMed
9.
Zurück zum Zitat Bergholdt R, Brorsson C, Palleja A, Berchtold LA, Fløyel T, Bang-Berthelsen CH, et al. Identification of novel type 1 diabetes candidate genes by integrating genome-wide association data, protein-protein interactions, and human pancreatic islet gene expression. Diabetes. 2012;61:954–62.CrossRefPubMedPubMedCentral Bergholdt R, Brorsson C, Palleja A, Berchtold LA, Fløyel T, Bang-Berthelsen CH, et al. Identification of novel type 1 diabetes candidate genes by integrating genome-wide association data, protein-protein interactions, and human pancreatic islet gene expression. Diabetes. 2012;61:954–62.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Ortutay C, Vihinen M. Identification of candidate disease genes by integrating gene ontologies and protein-interaction networks: case study of primary immunodeficiencies. Nucleic Acids Res. 2009;37:622–8.CrossRefPubMed Ortutay C, Vihinen M. Identification of candidate disease genes by integrating gene ontologies and protein-interaction networks: case study of primary immunodeficiencies. Nucleic Acids Res. 2009;37:622–8.CrossRefPubMed
11.
Zurück zum Zitat Shikha V, Ganesh B. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis. PLoS One. 2012;7:e49401.CrossRef Shikha V, Ganesh B. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis. PLoS One. 2012;7:e49401.CrossRef
12.
Zurück zum Zitat Hindumathi V, Kranthi T, Rao SB, Manimaran P. The prediction of candidate genes for cervix related cancer through gene ontology and graph theoretical approach. Mol Biosyst. 2014;10:1450–60.CrossRefPubMed Hindumathi V, Kranthi T, Rao SB, Manimaran P. The prediction of candidate genes for cervix related cancer through gene ontology and graph theoretical approach. Mol Biosyst. 2014;10:1450–60.CrossRefPubMed
13.
Zurück zum Zitat Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al. Genome-wide association study and meta-analysis finds over 40 loci affect risk of type 1 diabetes Nat. Genet. 2009;41:703–7. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al. Genome-wide association study and meta-analysis finds over 40 loci affect risk of type 1 diabetes Nat. Genet. 2009;41:703–7.
14.
Zurück zum Zitat Collins TK, Houghten S. A centrality based multi-objective approach to disease gene association. BioSystems. 2020;193–194:104133.CrossRefPubMed Collins TK, Houghten S. A centrality based multi-objective approach to disease gene association. BioSystems. 2020;193–194:104133.CrossRefPubMed
15.
Zurück zum Zitat Becker KG, Barnes KC, Bright TJ, Wang SA, et al. The Genetic Association Database. Nat Genet. 2004;36:431–2.CrossRefPubMed Becker KG, Barnes KC, Bright TJ, Wang SA, et al. The Genetic Association Database. Nat Genet. 2004;36:431–2.CrossRefPubMed
16.
Zurück zum Zitat Wang E, Zou J, Zaman N, Beitel LK, Trifiro M, Paliouras M, et al. Cancer systems biology in the genome sequencing era. Part 2. Evolutionary dynamics of tumor clonal networks and drug resistance. Semin Cancer Biol. 2013;23:286–92.CrossRefPubMed Wang E, Zou J, Zaman N, Beitel LK, Trifiro M, Paliouras M, et al. Cancer systems biology in the genome sequencing era. Part 2. Evolutionary dynamics of tumor clonal networks and drug resistance. Semin Cancer Biol. 2013;23:286–92.CrossRefPubMed
18.
Zurück zum Zitat Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2006;25:25–9.CrossRef Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2006;25:25–9.CrossRef
19.
Zurück zum Zitat Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z, et al. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10:48.CrossRefPubMedPubMedCentral Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z, et al. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10:48.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Kann MG. Advances in translational bioinformatics: computational approaches for the hunting of disease genes. Brief Bioinform. 2010;11:96–110.CrossRefPubMed Kann MG. Advances in translational bioinformatics: computational approaches for the hunting of disease genes. Brief Bioinform. 2010;11:96–110.CrossRefPubMed
23.
Zurück zum Zitat Kobayashi N, et al. CD44 variant inhibits insulin secretion in pancreatic β cells by attenuating LAT1-mediated amino acid uptake. Sci Rep. 2018;8:2785.CrossRefPubMedPubMedCentral Kobayashi N, et al. CD44 variant inhibits insulin secretion in pancreatic β cells by attenuating LAT1-mediated amino acid uptake. Sci Rep. 2018;8:2785.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Weiss L, Slavin S, Reich S, Cohen P, Shuster S, Stern R, et al. Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody. Proc Natl Acad Sci U S A. 2000;97:285–90.CrossRefPubMedPubMedCentral Weiss L, Slavin S, Reich S, Cohen P, Shuster S, Stern R, et al. Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody. Proc Natl Acad Sci U S A. 2000;97:285–90.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Gu HF, Zheng X, Abu Seman N, Gu T, Botusan IR, Sunkari VG, et al. Impact of the hypoxiainducible factor-1 a (HIF1A) Pro582Ser polymorphism on diabetes nephropathy. Diabetes Care. 2013;36:415–21.CrossRefPubMedPubMedCentral Gu HF, Zheng X, Abu Seman N, Gu T, Botusan IR, Sunkari VG, et al. Impact of the hypoxiainducible factor-1 a (HIF1A) Pro582Ser polymorphism on diabetes nephropathy. Diabetes Care. 2013;36:415–21.CrossRefPubMedPubMedCentral
26.
27.
Zurück zum Zitat Nomoto H, et al. Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes. Diabetologia. 2020;63:149–61.CrossRefPubMed Nomoto H, et al. Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes. Diabetologia. 2020;63:149–61.CrossRefPubMed
28.
Zurück zum Zitat Sarah EE, Ruan Q, Yang P, Zheng W, McIndoe RA, She JX. Gene expression profiles define a key checkpoint for type 1 diabetes in NOD mice. Diabetes. 2004;53:366–75.CrossRef Sarah EE, Ruan Q, Yang P, Zheng W, McIndoe RA, She JX. Gene expression profiles define a key checkpoint for type 1 diabetes in NOD mice. Diabetes. 2004;53:366–75.CrossRef
30.
Zurück zum Zitat Zhao Y, Krishnamurthy B, Mollah ZU, Kay TW, Thomas HE, et al. NF-κB in type 1 diabetes. Inflamm Allergy Drug Targets. 2011;10:208–17.CrossRefPubMed Zhao Y, Krishnamurthy B, Mollah ZU, Kay TW, Thomas HE, et al. NF-κB in type 1 diabetes. Inflamm Allergy Drug Targets. 2011;10:208–17.CrossRefPubMed
31.
Zurück zum Zitat Duggan BM, et al. RIPK2 dictates insulin responses to tyrosine kinase inhibitors in obese male mice. Endocrinology. 2020;161:bqaa086.CrossRefPubMed Duggan BM, et al. RIPK2 dictates insulin responses to tyrosine kinase inhibitors in obese male mice. Endocrinology. 2020;161:bqaa086.CrossRefPubMed
32.
Zurück zum Zitat Yang Y, et al. Associations between TNFSF4 gene polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and susceptibility to autoimmune diseases in Asians: a meta-analysis. Immunol Invest. 2020;24:1–17. Yang Y, et al. Associations between TNFSF4 gene polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and susceptibility to autoimmune diseases in Asians: a meta-analysis. Immunol Invest. 2020;24:1–17.
33.
Zurück zum Zitat Cortini A, et al. B cell OX40L supports T follicular helper cell development and contributes to SLE pathogenesis. Ann Rheum Dis. 2017;76:2095–103.CrossRefPubMed Cortini A, et al. B cell OX40L supports T follicular helper cell development and contributes to SLE pathogenesis. Ann Rheum Dis. 2017;76:2095–103.CrossRefPubMed
34.
Zurück zum Zitat Li Y, Cheng H, Zuo XB, Sheng YJ, Zhou FS, Tang XF, Tang HY, Gao JP, Zhang Z, He SM, Lv YM, Zhu KJ, Hu DY, Liang B, Zhu J, Zheng XD, Sun LD, Yang S, Cui Y, Liu JJ, Zhang XJ. Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population. J Med Genet. 2013;50:812–8. https://doi.org/10.1136/jmedgenet-2013-101787.CrossRefPubMed Li Y, Cheng H, Zuo XB, Sheng YJ, Zhou FS, Tang XF, Tang HY, Gao JP, Zhang Z, He SM, Lv YM, Zhu KJ, Hu DY, Liang B, Zhu J, Zheng XD, Sun LD, Yang S, Cui Y, Liu JJ, Zhang XJ. Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population. J Med Genet. 2013;50:812–8. https://​doi.​org/​10.​1136/​jmedgenet-2013-101787.CrossRefPubMed
35.
Zurück zum Zitat Sun XX, Li SS, Zhang M, et al. Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province. Am J Clin Exp Immunol. 2018;7:27–39.PubMedPubMedCentral Sun XX, Li SS, Zhang M, et al. Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province. Am J Clin Exp Immunol. 2018;7:27–39.PubMedPubMedCentral
38.
Zurück zum Zitat Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, Takada H, Hara T, Kawamura N, Ariga T, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. 2006;25:745–55.CrossRefPubMed Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, Takada H, Hara T, Kawamura N, Ariga T, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. 2006;25:745–55.CrossRefPubMed
40.
Zurück zum Zitat Wu Z, Li J, Zhang Y, Hu L, Peng X. CFTR regulates the proliferation, migration and invasion of cervical cancer cells by inhibiting the NF-κB signalling pathway. Cancer Manag Res. 2020;12:4685–97.CrossRefPubMedPubMedCentral Wu Z, Li J, Zhang Y, Hu L, Peng X. CFTR regulates the proliferation, migration and invasion of cervical cancer cells by inhibiting the NF-κB signalling pathway. Cancer Manag Res. 2020;12:4685–97.CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Zhu F, Shi Z, Qin C, Tao L, Liu X, Xu F, et al. Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012;40:D1128–36.CrossRefPubMed Zhu F, Shi Z, Qin C, Tao L, Liu X, Xu F, et al. Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012;40:D1128–36.CrossRefPubMed
Metadaten
Titel
A graph centrality-based approach for candidate gene prediction for type 1 diabetes
verfasst von
N. B. Thummadi
E. Vishnu
E. V. Subbiah
P. Manimaran
Publikationsdatum
23.07.2021
Verlag
Springer US
Erschienen in
Immunologic Research / Ausgabe 5/2021
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-021-09217-0

Weitere Artikel der Ausgabe 5/2021

Immunologic Research 5/2021 Zur Ausgabe

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

HNO-Op. auch mit über 90?

16.04.2024 HNO-Chirurgie Nachrichten

Mit Blick auf das Risiko für Komplikationen nach elektiven Eingriffen im HNO-Bereich scheint das Alter der Patienten kein ausschlaggebender Faktor zu sein. Entscheidend ist offenbar, wie fit die Betroffenen tatsächlich sind.

Intrakapsuläre Tonsillektomie gewinnt an Boden

16.04.2024 Tonsillektomie Nachrichten

Gegenüber der vollständigen Entfernung der Gaumenmandeln hat die intrakapsuläre Tonsillektomie einige Vorteile, wie HNO-Fachleute aus den USA hervorheben. Sie haben die aktuelle Literatur zu dem Verfahren gesichtet.

Bilateraler Hörsturz hat eine schlechte Prognose

15.04.2024 Hörsturz Nachrichten

Die Mehrzahl der Menschen mit Hörsturz ist einseitig betroffen, doch auch ein beidseitiger Hörsturz ist möglich. Wie häufig solche Fälle sind und wie sich ihr Verlauf darstellt, hat eine HNO-Expertenrunde aus den USA untersucht.

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.