Sara E Grineski, Danielle X Morales, Timothy W Collins
Modifying Summer Undergraduate Research Programs during COVID-19 Increased Graduate School Intentions but Exacerbated Anxieties
CBE life sciences education
elucidating compound mechanism action moa beneficial drug discovery practice often represents significant challenge causal reasoning approaches aim address situation inferring dysregulated signalling proteins using transcriptomics data biological networks however comprehensive benchmarking approaches yet reported benchmarked four causal reasoning algorithms signet causalr causalr scanr carnival four networks smaller omnipath network vs 3 larger metabase networks using lincs l1000 cmap microarray data assessed extent factor dictated successful recovery direct targets compoundassociated signalling pathways benchmark dataset comprising 269 compounds additionally examined impact performance terms functions roles protein targets connectivity bias prior knowledge networks according statistical analysis negative binomial model combination algorithm network significantly dictated performance causal reasoning algorithms signet recovering greatest number direct targets respect recovery signalling pathways carnival omnipath network able recover informative pathways containing compound targets based reactome pathway hierarchy additionally carnival signet causalr scanr outperformed baseline gene expression pathway enrichment results found significant difference performance l1000 data microarray data even limited 978 landmark genes notably causal reasoning algorithms also outperformed pathway recovery based input degs despite often used pathway enrichment causal reasoning methods performance somewhat correlated connectivity biological role targets overall conclude causal reasoning performs well recovering signalling proteins related compound moa upstream gene expression changes leveraging prior knowledge networks choice network algorithm profound impact performance causal reasoning algorithms based analyses presented true microarraybased gene expression data well based l1000 platform