CoV-Hipathia

CoV-Hipathia models human signaling pathway activity and simulates drug and mutation effects to interpret molecular mechanisms of SARS-CoV-2 infection.


Key Features:

  • Mechanistic modeling: Implements mechanistic models of signaling circuits involved in SARS-CoV-2 infection, including pathways related to viral entry, replication, inflammation, and antigenic response.
  • Gene expression inference: Infers human signaling activity from gene expression data to assess how expression changes impact cellular responses during infection.
  • Genomic mutation analysis: Interprets the impact of genomic mutations on signaling pathways and cellular mechanisms relevant to SARS-CoV-2.
  • Intervention simulation: Simulates interventions such as gene knock-downs and drug effects, modeling over 8,000 drugs from DrugBank.
  • Graph-based analysis: Provides graph-based disease modeling by integrating curated pathway diagrams with interaction and text-mining databases as part of the COVID-19 Disease Map (C19DMap) initiative.
  • C19DMap integration: Leverages the curated dataset and computable repository from the COVID-19 Disease Map project for pathway and mechanism interpretation.

Scientific Applications:

  • Antiviral candidate discovery: Supports identification and prioritization of potential antiviral drugs by simulating drug effects on signaling pathways.
  • Therapeutic target identification: Aids identification of molecular targets by revealing pathway nodes and circuits altered by infection or mutation.
  • Biomarker and signature discovery: Enables detection of gene expression and mutation signatures related to SARS-CoV-2 predisposition and treatment response.
  • Hypothesis generation on virus-host interactions: Facilitates proposal of testable hypotheses about mechanisms of SARS-CoV-2 invasion and host cellular consequences via graph-based analyses.

Methodology:

Integrates curated knowledge from the COVID-19 Disease Map (C19DMap) and literature by curating pathway diagrams and linking them with interaction and text-mining databases; infers signaling activity from gene expression and genomic mutation data; performs graph-based analyses and simulates interventions including gene knock-downs and DrugBank drug effects.

Topics

Collections

Details

Maturity:
Mature
Cost:
Free of charge
Tool Type:
web application
Operating Systems:
Mac, Linux, Windows
Programming Languages:
JavaScript, R, SQL
Added:
3/11/2022
Last Updated:
3/14/2022

Operations

Publications

Rian K, Esteban-Medina M, Hidalgo MR, Çubuk C, Falco MM, Loucera C, Gunyel D, Ostaszewski M, Peña-Chilet M, Dopazo J. Mechanistic modeling of the SARS-CoV-2 disease map. BioData Mining. 2021;14(1). doi:10.1186/s13040-021-00234-1. PMID:33478554. PMCID:PMC7817765.

PMID: 33478554
PMCID: PMC7817765
Funding: - Ministerio de Economía y Competitividad: SAF2017-88908-R - Instituto de Salud Carlos III: ACCI2018/29, COV20/00788, PT17/0009/0006 - FP7 People: Marie-Curie Actions: 813533

Ostaszewski M, Niarakis A, Mazein A, Kuperstein I, Phair R, Orta‐Resendiz A, Singh V, Aghamiri SS, Acencio ML, Glaab E, Ruepp A, Fobo G, Montrone C, Brauner B, Frishman G, Monraz Gómez LC, Somers J, Hoch M, Kumar Gupta S, Scheel J, Borlinghaus H, Czauderna T, Schreiber F, Montagud A, Ponce de Leon M, Funahashi A, Hiki Y, Hiroi N, Yamada TG, Dräger A, Renz A, Naveez M, Bocskei Z, Messina F, Börnigen D, Fergusson L, Conti M, Rameil M, Nakonecnij V, Vanhoefer J, Schmiester L, Wang M, Ackerman EE, Shoemaker JE, Zucker J, Oxford K, Teuton J, Kocakaya E, Summak GY, Hanspers K, Kutmon M, Coort S, Eijssen L, Ehrhart F, Rex DAB, Slenter D, Martens M, Pham N, Haw R, Jassal B, Matthews L, Orlic‐Milacic M, Senff-Ribeiro A, Rothfels K, Shamovsky V, Stephan R, Sevilla C, Varusai T, Ravel J, Fraser R, Ortseifen V, Marchesi S, Gawron P, Smula E, Heirendt L, Satagopam V, Wu G, Riutta A, Golebiewski M, Owen S, Goble C, Hu X, Overall RW, Maier D, Bauch A, Gyori BM, Bachman JA, Vega C, Grouès V, Vazquez M, Porras P, Licata L, Iannuccelli M, Sacco F, Nesterova A, Yuryev A, de Waard A, Turei D, Luna A, Babur O, Soliman S, Valdeolivas A, Esteban‐Medina M, Peña‐Chilet M, Rian K, Helikar T, Puniya BL, Modos D, Treveil A, Olbei M, De Meulder B, Ballereau S, Dugourd A, Naldi A, Noël V, Calzone L, Sander C, Demir E, Korcsmaros T, Freeman TC, Augé F, Beckmann JS, Hasenauer J, Wolkenhauer O, Willighagen EL, Pico AR, Evelo CT, Gillespie ME, Stein LD, Hermjakob H, D'Eustachio P, Saez‐Rodriguez J, Dopazo J, Valencia A, Kitano H, Barillot E, Auffray C, Balling R, Schneider R. COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms. Molecular Systems Biology. 2021;17(10). doi:10.15252/msb.202110387. PMID:34664389. PMCID:PMC8524328.

PMID: 34664389
PMCID: PMC8524328
Funding: - Fonds National de la Recherche Luxembourg: COVID‐19/2020‐1/14715687/CovScreen - H2020 LEIT Information and Communication Technologies: H2020‐ICT‐825070, H2020‐ICT‐951773 - Deutsches Zentrum für Infektionsforschung: 8020708703 - Association Nationale de la Recherche et de la Technologie: 2020/0766 - H2020 Marie Skłodowska-Curie Actions: 765274

Ostaszewski M, Mazein A, Gillespie ME, Kuperstein I, Niarakis A, Hermjakob H, Pico AR, Willighagen EL, Evelo CT, Hasenauer J, Schreiber F, Dräger A, Demir E, Wolkenhauer O, Furlong LI, Barillot E, Dopazo J, Orta-Resendiz A, Messina F, Valencia A, Funahashi A, Kitano H, Auffray C, Balling R, Schneider R. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms. Scientific Data. 2020;7(1). doi:10.1038/s41597-020-0477-8. PMID:32371892. PMCID:PMC7200764.

Documentation

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