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Record W4391783806 · doi:10.3389/fimmu.2023.1282859

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

2024· article· en· W4391783806 on OpenAlexaff
Anna Niarakis, Marek Ostaszewski, Alexander Mazein, Inna Kuperstein, Martina Kutmon, Marc Gillespie, Akira Funahashi, Márcio Luís Acencio, Ahmed Abdelmonem Hemedan, Michael Aichem, Karsten Klein, Tobias Czauderna, Felicia Burtscher, Takahiro Yamada, Yusuke Hiki, Noriko Hiroi, Finterly Hu, Nhung Pham, Friederike Ehrhart, Egon Willighagen, Alberto Valdeolivas, Aurélien Dugourd, Francesco Messina, Marina Esteban‐Medina, María Peña-Chilet, Kinza Rian, Sylvain Soliman, Sara Sadat Aghamiri, Bhanwar Lal Puniya, Aurélien Naldi, Tomáš Helikar, Vidisha Singh, Marco Fariñas Fernández, Viviam Bermudez, Eirini Tsirvouli, Arnau Montagud, Vincent Noël, Miguel Ponce-de-León, Dieter Maier, Angela Bauch, Benjamin M. Gyori, John A. Bachman, Augustin Luna, Janet Piñero, Laura I. Furlong, Irina Balaur, Adrien Rougny, Yohan Jarosz, Rupert W. Overall, Robert D. Phair, Livia Perfetto, Lisa Matthews, Marija Orlic-Milacic, Luis Cristóbal Monraz Gómez, Bertrand De Meulder, Jean‐Marie Ravel, Bijay Jassal, Venkata Satagopam, Guanming Wu, Martin Golebiewski, Piotr Gawron, Laurence Calzone, J. Beckmann, Chris T. Evelo, Peter D’Eustachio, Falk Schreiber, Julio Sáez-Rodríguez, Joaquı́n Dopazo, Martin Kuiper, Alfonso Valencia, Olaf Wolkenhauer, Hiroaki Kitano, Emmanuel Barillot, Charles Auffray, Rudi Balling, Reinhard Schneider

Bibliographic record

VenueFrontiers in Immunology · 2024
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsOntario Institute for Cancer Research
FundersNational Institute of General Medical SciencesZonMw
KeywordsRepurposingDrug repositioningContext (archaeology)Identification (biology)InteroperabilityComputer scienceComputational biologySystems biologyData scienceCoronavirus disease 2019 (COVID-19)Drug discoveryKey (lock)DrugDiseaseBioinformaticsInfectious disease (medical specialty)BiologyMedicineWorld Wide WebPharmacology

Abstract

fetched live from OpenAlex

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.048
GPT teacher head0.314
Teacher spread0.266 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations21
Published2024
Admission routes1
Has abstractyes

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