TY - GEN
T1 - Predicting Cellular Responses to Novel Drug Perturbations at a Single-Cell Resolution
AU - Hetzel, Leon
AU - Böhm, Simon
AU - Kilbertus, Niki
AU - Günnemann, Stephan
AU - Lotfollahi, Mohammad
AU - Theis, Fabian
N1 - Publisher Copyright:
© 2022 Neural information processing systems foundation. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.
AB - Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.
UR - http://www.scopus.com/inward/record.url?scp=85161650838&partnerID=8YFLogxK
M3 - Conference contribution
AN - SCOPUS:85161650838
T3 - Advances in Neural Information Processing Systems
BT - Advances in Neural Information Processing Systems 35 - 36th Conference on Neural Information Processing Systems, NeurIPS 2022
A2 - Koyejo, S.
A2 - Mohamed, S.
A2 - Agarwal, A.
A2 - Belgrave, D.
A2 - Cho, K.
A2 - Oh, A.
PB - Neural information processing systems foundation
T2 - 36th Conference on Neural Information Processing Systems, NeurIPS 2022
Y2 - 28 November 2022 through 9 December 2022
ER -