SLKB: synthetic lethality kno wledg e base

Abstract

Emerging CRISPR-Cas9 technology permits synthetic lethality (SL) screening of large number of gene pairs from gene combination double knock out (CDKO) e xperiments. Ho w e v er, the poor integration and annotation of CDKO SL dat a in current SL dat abases limit their utilit y, and diverse methods of calculating SL scores prohibit their comparison. To o v ercome these shortcomings, w e ha v e de v eloped SL kno wledge base (SLKB) that incorporates data of 11 CDKO experiments in 22 cell lines, 16,059 SL gene pairs and 264,424 non-SL gene pairs. Additionally, within SLKB, w e ha v e implemented fiv e SL calculation methods: median score with and without background control normalization (Median-B / NB), sgRNA-derived score (sgRNA-B / NB), Horlbeck score, GEMINI score and MAGeCK score. The five scores have demonstrated a mere 1.21% o v erlap among their top 10% SL gene pairs, reflecting high diversity. Users can browse SL networks and assess the impact of scoring methods using Venn diagrams. The SL network generated from all data in SLKB shows a greater likelihood of SL gene pair connectivity with other SL gene pairs than non-SL pairs. Comparison of SL networks between two cell lines demonstrated greater likelihood to share SL hub genes than SL gene pairs. SLKB website and pipeline can be freely accessed at https://slkb.osubmi.org and https:// slkb.docs.osubmi.org/ , respectively.