Authors
Xiaojie Qiu, Yan Zhang, Jorge D Martin-Rufino, Chen Weng, Shayan Hosseinzadeh, Dian Yang, Angela N Pogson, Marco Y Hein, Kyung Hoi Joseph Min, Li Wang, Emanuelle I Grody, Matthew J Shurtleff, Ruoshi Yuan, Song Xu, Yian Ma, Joseph M Replogle, Eric S Lander, Spyros Darmanis, Ivet Bahar, Vijay G Sankaran, Jianhua Xing, Jonathan S Weissman
Publication date
2022/2/1
Journal
Cell
Publisher
Cell Press
Description
Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte …
Total citations
202120222023202410429566
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