Interrogation of genome-wide, experimentally dissected gene regulatory networks reveals mechanisms underlying dynamic cellular state control
Tan, X.; Worley, J.; Turunen, M.; Wong, K.; Fernandez, E. C.; Paull, E.; Jones, S.; Wang, J.; Noh, H.; Salvatori, B.; Chavez, A.; Califano, A.
Show abstract
Pooled CRISPRi-mediated silencing of >1,000 transcriptional regulators expressed in single colorectal adenocarcinoma cells, followed by single-cell RNA-seq profiling at two timepoints, 1 day and 4 days, allowed reverse engineering the underlying tumor context-specific, causal regulatory network. Furthermore, the availability of experimentally derived, highly multiplexed gene reporter assays for each regulator, as identified by this analysis, allowed accurate assessment of differential protein activity following silencing of each regulator, thus providing proof-of-concept for generating comprehensive, tissue-specific networks of transcriptional and post-translational interactions. Analysis of this causal network allowed elucidation of complex autoregulatory mechanisms that have eluded previous computational approaches and supported systematic elucidation of cooperative mechanisms, where one regulatory protein can modulate the activity of another regulatory protein, as well as transcriptional mimicry, where one regulatory protein can phenocopy others.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- A single-cell transcriptomics CRISPR-activation screen identifies new epigenetic regulators of zygotic genome activation 96%
- Comprehensive prediction of robust synthetic lethality between paralog pairs in cancer cell lines 95%
- Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome 95%
Similar papers in this journal
- Identifying transcription factor-bound gene activators and silencers in the chromatin accessible human genome using ATAC-STARR-seq 96%
- Trading Genome Vulnerability for Stable Genetic Inheritance: Active Retrotransposons Help Maintain Pericentromeric Heterochromatin Required for Faithful Cell Division 96%
- Enhancers display constrained sequence flexibility and context-specific modulation of motif function 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.