It is demonstrated that machine learning applied to transcriptomic data can uncover novel cancer vulnerabilities and actionable targets in individual tumors, even in the absence of functional screening, which may represent a scalable approach to advance precision oncology in rare and/or under-characterized cancer types.
Ananthan Sadagopan, Bingchen Li, Jiao Li et al.· Cancer Research· 0 citations
An selective, on-target, and well-tolerated DHODH inhibitor, GLIO-1, that is effective in IDH-mutant gliomas is developed and nominated as a new pan-cancer biomarker and targeted therapy pairing, KDM6A inactivation and GLIO-1, that is poised for clinical translation.
Alexander C-Y. Tsai, Mathew D. Lin, V. Puliyappadamba et al.· Clinical Cancer Research· 0 citations
An selective, on-target, and well-tolerated DHODH inhibitor, GLIO-1, that is effective in IDH-mutant gliomas is developed and nominated as a new pan-cancer biomarker and targeted therapy pairing, KDM6A inactivation and GLIO-1, that is poised for clinical translation.
Alexander C-Y. Tsai, Mathew D. Lin, V. Puliyappadamba et al.· Clinical Cancer Research· 0 citations
CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread adoption. Here, we establish benchmarking libraries for Cas9-based CRISPRko and CRISPRi screens using Perturb-seq as the read-out. For both modalities, we observe consistent transcriptional signatures among cells with the same genes perturbed, strong evidence of on-target signal. We also examine tradeoffs between modalities: while CRISPRi guides demonstrate heightened rates of off-target activity, we also observe artifacts stemming from the cellular response to double-stranded breaks with the use of CRISPRko. The libraries and analyses presented here will be a useful benchmarking and de-risking resource for any group preparing for a large-scale Perturb-seq screen.
Laura M Drepanos, Berta Escude Velasco, Abigail J Chase et al.· bioRxiv· 1 citation
This work compares the performance of multiple KRAB domain systems, develops an updated CRISPRi-specific on-target scoring scheme, and quantitatively characterize off-target effects associated with seed-sequence patterns.
Smriti Srikanth, Fengyi Zheng, Laura M Drepanos et al.· Cell Genomics· 0 citations
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