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Harm Ledger · provisional · Biology

Genome-scale perturbation signatures from primary human CD4+ T cells improve genetics-based prioritization of immune drug targets

While human genetic evidence improves drug program success, target selection largely relies on associational features. Even functional features are mainly observational, capturing disease associations rather than the consequence of perturbing genes in the disease-relevant human cell type. To move beyond association, we present IGNITE (Immune Genomics and fuNctional Integration for Target Enrichment), a framework that prioritizes immune drug targets by integrating human genetic priors with features from genome-scale perturb-seq in 22 million primary human CD4+ T cells and polarized T-helper sub

Tier 1 Limited HarmMethodology 0.2
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1 base · Limited Harm (tier 1 of 5, 1 pts)
× 0.1000 attribution · Minor documented assistance
× 0.5000 evidence · External expert evaluation
× 0.2000 realization · Proposed
× 0.5000 durability · Medium-term
Event-level product before credit split: 0.01

Ingest update: independent source raised evidence; added a follow-up source. Score remains provisional until review. Follow-up ingest: independent source raised evidence; added a follow-up source. Follow-up ingest: independent source raised evidence; added a follow-up source. Follow-up ingest: independent source raised evidence; added a follow-up source.

What happened

While human genetic evidence improves drug program success, target selection largely relies on associational features. Even functional features are mainly observational, capturing disease associations rather than the consequence of perturbing genes in the disease-relevant human cell type. To move beyond association, we present IGNITE (Immune Genomics and fuNctional Integration for Target Enrichment), a framework that prioritizes immune drug targets by integrating human genetic priors with features from genome-scale perturb-seq in 22 million primary human CD4+ T cells and polarized T-helper subset differential expression. IGNITE is a semi-supervised machine learning model that applies positive-unlabeled learning to approved immune targets, then ranks 19,502 protein-coding genes to prioritize new candidates. In 727 in-trial genes held out from training, functional genomics increased target enrichment among the top 50 nominations from 2.7- to 4.8-fold for immune trial targets at any phase, and from 4.5- to 5.9-fold for targets in Phase III. These performance gains were immune-specific, as IGNITE outperformed genetic comparators on predicting immune-exclusive targets but not on cardiac-exclusive targets. Using temporal validation with labels frozen in 2014, IGNITE outperformed the genetics-only model in ranking 134 genes that subsequently entered immune trials. The functional genomics layer also surfaced two novel, pharmacologically tractable candidates, ELOVL6 and RUVBL1, elevating their rankings from outside the top 1,000 into the top 50. These findings highlight that perturbational signatures in the disease-relevant human cell type harbor target-relevant signals beyond human genetics, offering a generalizable route to indication-specific prioritization as perturbation atlases expand. Full IGNITE scores are publicly available at https://ignite.eecs.umich.edu/ Update (2026-09-08): Funding grants for new research into AI and teen development. Apply now for OpenAI’s $5 million grant program supporting independent research on how generative AI affects teen development, well-being, and safety. Update (2026-09-18): EXCLUSIVE: Anthropic quietly sets up biology lab as it ramps AI drug program - Reuters. EXCLUSIVE: Anthropic quietly sets up biology lab as it ramps AI drug program  Reuters Update (2026-09-20): BRIDGE-AD reveals Alzheimer's disease effectors through interpretable large-scale omics integration . The growing landscape of Alzheimer's disease (AD) datasets creates opportunities to integrate heterogeneous evidence and systematically discover disease effectors. We present BRIDGE-AD, an interpretable network medicine framework that transforms multimodal data into a unified, disease-specific gene representation for AD effector prioritisation. We integrated more than 30 datasets and curated resources spanning omics, functional, genetic and prior disease knowledge layers. BRIDGE-AD outperformed recently published pretrained and modality-specific gene embeddings in recovering AD-associated genes and produced a genome-wide resource of candidate AD effectors. Established and newly prioritised effectors formed 19 functional clusters, revealing a global molecular landscape of AD biology. BRIDGE-AD supported an SPP1-centred cross-compartment hypothesis and nominated SCARB2, a poorly characterised candidate, for functional validation. SCARB2 rewired lysosomal, lipid-handling and autophagic programmes in microglia, whereas disrupted SCARB2 glycosylation in AD imp Update (2026-09-23): Offloaded inference for real-world physical AI robotics. Robots are getting smarter, but how can their hardware match that growth? New Microsoft Research findings show that moving AI inference beyond the robot can improve task success, boost efficiency, and support more advanced physical AI workloads. The post Offloaded inference for real-world physical AI robotics appeared first on Microsoft Research.

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Claims

  • Genome-scale perturbation signatures from primary human CD4+ T cells improve genetics-based prioritization of immune drug targets

    outcome · supported

Sources

Revision history

  • 16 Sep 2026 · 0.00 → 0.00

    Auto-published from news ingest.

  • 17 Sep 2026 · 0.00 → 0.00

    Ingest update: independent source raised evidence; added a follow-up source.

  • 18 Sep 2026 · 0.00 → 0.00

    Ingest update: independent source raised evidence; added a follow-up source.

  • 20 Sep 2026 · 0.00 → 0.00

    Ingest update: independent source raised evidence; added a follow-up source.

  • 23 Sep 2026 · 0.00 → 0.01

    Ingest update: independent source raised evidence; added a follow-up source.