CODEX: COunterfactual Deep learning for the in-silico EXploration of cancer cell line perturbations

Tallennettuna:
Bibliografiset tiedot
Julkaisussa:bioRxiv (Jan 29, 2024)
Päätekijä: Schrod, Stefan
Muut tekijät: Zacharias, Helena U, Beissbarth, Tim, Hauschild, Anne-Christin, Altenbuchinger, Michael Christoph
Julkaistu:
Cold Spring Harbor Laboratory Press
Aiheet:
Linkit:Citation/Abstract
Full Text - PDF
Full text outside of ProQuest
Tagit: Lisää tagi
Ei tageja, Lisää ensimmäinen tagi!

MARC

LEADER 00000nab a2200000uu 4500
001 2919548584
003 UK-CbPIL
022 |a 2692-8205 
024 7 |a 10.1101/2024.01.24.577020  |2 doi 
035 |a 2919548584 
045 0 |b d20240129 
100 1 |a Schrod, Stefan 
245 1 |a CODEX: COunterfactual Deep learning for the in-silico EXploration of cancer cell line perturbations 
260 |b Cold Spring Harbor Laboratory Press  |c Jan 29, 2024 
513 |a Working Paper 
520 3 |a Motivation: High-throughput screens (HTS) provide a powerful tool to decipher the causal effects of chemical and genetic perturbations on cancer cell lines. Their ability to evaluate a wide spectrum of interventions, from single drugs to intricate drug combinations and CRISPR interference, has established them as an invaluable resource for the development of novel therapeutic approaches. Nevertheless, the combinatorial complexity of potential interventions makes a comprehensive exploration intractable. Hence, prioritizing interventions for further experimental investigation becomes of utmost importance. Results: We propose CODEX as a general framework for the causal modeling of HTS data, linking perturbations to their downstream consequences. CODEX relies on a stringent causal modeling strategy based on counterfactual reasoning. As such, CODEX predicts drug-specific cellular responses, comprising cell survival and molecular alterations, and facilitates the in-silico exploration of drug combinations. This is achieved for both bulk and single-cell HTS. We further show that CODEX provides a rationale to explore complex genetic modifications from CRISPR-interference in silico in single cells. Availability and Implementation: Our implementation of CODEX is publicly available at https://github.com/sschrod/CODEX. All data used in this article are publicly available.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://github.com/sschrod/CODEX 
653 |a Tumor cell lines 
653 |a CRISPR 
653 |a Deep learning 
653 |a Cell survival 
700 1 |a Zacharias, Helena U 
700 1 |a Beissbarth, Tim 
700 1 |a Hauschild, Anne-Christin 
700 1 |a Altenbuchinger, Michael Christoph 
773 0 |t bioRxiv  |g (Jan 29, 2024) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/2919548584/abstract/embedded/H09TXR3UUZB2ISDL?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/2919548584/fulltextPDF/embedded/H09TXR3UUZB2ISDL?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2024.01.24.577020v1