PerturbGate

PerturbGate is an open-data, reproducible pipeline that turns a genome-scale primary human CD4 T-cell Perturb-seq screen into evidence-gated mechanism hypotheses — not another ranking of hits. Each of 924 knockdowns is scored not by "does the cell change?" but by "does it reverse a donor-paired juvenile-arthritis disease direction?", then put through gates for technical validity, disease direction, an external patient cohort, and translatability. The result is an honest triad: PAK2, a strong reproducible cellular hit, was rejected as non-directional; RIPK1 is an unsupported comparator; RICTOR reverses the inflamed T-cell programme (+0.161 internal, +0.165 in an independent JIA cohort, 6/6 leave-one-donor-out) but is retained only as a mechanism hypothesis with an explicit modality gap - never a validated target. Every number resolves to a committed frozen table; negatives and corrected results are first-class outputs. It recomputes on a laptop in minutes.