Ranking Reprogramming Factors for Directed Differentiation
Ranking Reprogramming Factors for Directed Differentiation
Abstract Transcription factor over-expression is a proven method for reprogramming cells to a desired cell type for regenerative medicine and therapeutic discovery. However, a general method for the identification of reprogramming factors to create an arbitrary cell type is an open problem. We examine the success rate of methods and data for directed differentiation by testing the ability of nine computational methods (CellNet, GarNet, EBSeq, AME, DREME, HOMER, KMAC, diffTF, and DeepAccess) to correctly discover and rank candidate factors for eight target cell types with known reprogramming solutions. We compare methods that utilize gene expression, biological networks, and chromatin accessibility data to identify eight sets of known reprogramming factors and comprehensively test parameter and pre-processing of input data to optimize performance of these methods. We find the best factor identification methods can identify an average of 50-60% of reprogramming factors within the top 10 candidates, and methods that use chromatin accessibility perform the best. Among the chromatin accessibility methods, complex methods DeepAccess and diffTF are more likely to consistently correctly rank the significance of transcription factor candidates within reprogramming protocols for differentiation. We provide evidence that AME and DeepAccess are optimal methods for transcription factor recovery and ranking which will allow for systematic prioritization of transcription factor candidates to aid in the design of novel reprogramming protocols.
Hammelman Jennifer、Patel Tulsi、Closser Michael、Gifford David、Wichterle Hynek
Computational and Systems Biology, MIT||Computer Science and Artificial Intelligence Laboratory, MITDepartments of Pathology & Cell Biology, Neuroscience, Rehabilitation and Regenerative Medicine (in Neurology), Columbia University Irving Medical Center||Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center||Columbia Stem Cell Initiative, Columbia University Irving Medical CenterDepartments of Pathology & Cell Biology, Neuroscience, Rehabilitation and Regenerative Medicine (in Neurology), Columbia University Irving Medical Center||Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center||Columbia Stem Cell Initiative, Columbia University Irving Medical CenterComputational and Systems Biology, MIT||Computer Science and Artificial Intelligence Laboratory, MIT||Department of Biological Engineering, MIT||Department of Electrical Engineering and Computer Science, MITDepartments of Pathology & Cell Biology, Neuroscience, Rehabilitation and Regenerative Medicine (in Neurology), Columbia University Irving Medical Center||Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center||Columbia Stem Cell Initiative, Columbia University Irving Medical Center
生物科学研究方法、生物科学研究技术基础医学分子生物学
Hammelman Jennifer,Patel Tulsi,Closser Michael,Gifford David,Wichterle Hynek.Ranking Reprogramming Factors for Directed Differentiation[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2021.05.14.444080.点此复制
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