Evidence map›Paper›PMID 42760254›Full record

ArticleBioinformatics (Oxford, England)2026

VCCV: conservative transcriptomic corroboration for measurement prioritization of computational drug-target hypotheses.

Haihui Huang, Yanan Zhou, Dingkui Kang, Yong Liang

Abstract read
In one paragraph

Article in Bioinformatics (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Haihui HuangShaoguan Research Center of the National Engineering Laboratory for Big Data System Computing Technology, Shaoguan University, Shaoguan, 512005, China.ORCID 0000-0002-6546-969X
Yanan ZhouShaoguan Research Center of the National Engineering Laboratory for Big Data System Computing Technology, Shaoguan University, Shaoguan, 512005, China.
Dingkui KangGuangdong Provincial Laboratory of Traditional Chinese Medicine, Hengqin, 519031, China.
Yong LiangGuangdong Provincial Laboratory of Traditional Chinese Medicine, Hengqin, 519031, China.

Funding

Chinese Medicine Guangdong Laboratory HQL2025SU008Guangdong Key Construction Discipline Research Capacity Enhancement 2022ZDJS049National Natural Science Foundation of China 62102261Natural Science Foundation of Guangdong Province 2026A1515010592
6 · The paper itself

Abstract

motivationComputational drug-target interaction (DTI) models nominate plausible binders but cannot determine which candidate best accounts for an observed cellular response. Perturbational transcriptomics offers orthogonal mechanistic evidence, yet pharmacology-to-genetics mismatch, incomplete reference coverage, and non-specific stress programs make simple signature matching unreliable. This motivates a principled integration layer that corroborates hypotheses conservatively, abstains under global mismatch, and prioritizes informative follow-up measurements when the evidence remains ambiguous.

resultsWe present Virtual-to-Cellular Corroboration for Validation (VCCV), a model-agnostic posterior-triage layer for pre-trained DTI models. VCCV updates calibrated DTI working weights with context-aligned perturbational evidence using a near-identity affine map and exact covariance transport. Within the stated Gaussian class, exact transport is the unique uncertainty update that preserves posterior-odds comparisons under invertible affine changes of measurement coordinates. VCCV also introduces an empirical warning branch for abstention and converts residual ambiguity into compact follow-up gene panels, using a submodular objective for deep near-ties. Each query is assigned one of three actionable states: a target-resolved hypothesis, an abstention, or a prioritized panel. Across five DTI models, VCCV improved discrimination (paired ROC-AUC gains 0.021-0.037) and reduced negative log-likelihood in every case. Additional evaluations showed improved ranking on the same-cell-supported endpoint, warning-score discrimination of strong-response profiles (ROC-AUC 0.876), and better recovery of full-coordinate leading hypotheses by selected panels than by random panels. Across these retrospective kinase-focused evaluations, VCCV provides a principled bridge from computational nomination to conservative, measurement-directed cellular corroboration. AVAILABILITY AND IMPLEMENTATION: Source code of VCCV is publicly available at https://github.com/bio-ai-source/VCCV.

Indexed as

Computational BiologyDrug DiscoverySoftwareTranscriptomeHumans

Identifiers

PMID42760254
PMCPMC13633670

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.