Title:  Cell Reprogramming and Digital Biology
Abstract:  In this talk, I will present our work on cell reprogramming. Within this work we developed an algorithm we call "data-guided control" (DGC) and a wiring diagram for the human genome we call the "hard-wired genome." The DGC algorithm predicts the genetic inputs necessary to convert one cell type (e.g., skin) directly into another (e.g., muscle) without first generating stem cells. I will present an example from our recent work on directly reprogramming human fibroblasts into hematopoietic stem cells. Additionally, I will discuss our DARPA-funded research, where we leverage foundation models in combination with DGC to refine predictions for direct cell reprogramming.

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• Chen H, Chen J, Muir LA, Ronquist S, Meixner W, Ljungman M, Ried T, Smale S, Rajapakse I. Functional Organization of the Human 4D Nucleome. Proceedings of the National Academy of Sciences 112.26 (2015): 8002-8007.
• C. Stansbury, J. Cwycyshyn, J. Pickard, W. Meixner, I. Rajapakse, and L. A. Muir, Data-guided direct reprogramming of human fibroblasts into the hematopoietic lineage, Aug. 26, 2024, bioRxiv
• Joshua Pickard, Ram Prakash, Marc Andrew Choi, Natalie Oliven, Cooper Stansbury, Jillian Cwycyshyn, Alex Gorodetsky, Alvaro Velasquez, and Indika Rajapakse, Language Model Powered Digital Biology with BRAD, arXiv preprint arXiv:2409.02864v3 (2024)
• Rajapakse I, and Smale S. Mathematics of the Genome. Foundations of Computational Mathematics 17.5 (2017): 1195-1217.