Fig. 3: Expert curation of recommended hits along with features used for hit triaging.

Evaluation of top recommended genes by five independent experts indicates that majority of genes can be classified either as A “known resistance markers” or C “previously unknown/less known, credible hits”. Eight genes were labeled as “previously unknown/less known hits with unclear tractability” by the experts (B). Here, unclear tractability refers to the absence of clear path to validate predictions experimentally. “Previously unknown/less known” is definned within the biological context of this study. Features used to generate predictions: full_screen—overall consistency across all conditions in the CRISPR screen; RNASeq_LFC-log2 fold-change from internal RNASeq study; clinical_ES1, clinical_ES2, clinical_ES3-enrichment scores from clinical studies where resistant patients were compared against responders; lit_EGFR, lit_NSCLC-co-occurrence estimates from the literature; pagerank—“popularity” measure of a node; betweenness—centrality estimate of a node. “Agreement” column indicates the number of experts assigning a certain label to a gene. Size of a bubble reflects value normalized across the full set of features for all genes.