STOR Colloquium: Geoffrey Schiebinger, MIT and Harvard
The Broad Institute of MIT and Harvard and
the MIT Statistics and Data Science Center
Towards a mathematical theory of development
In this talk we introduce a mathematical model to describe temporal processes like embryonic development and cellular reprogramming. We consider stochastic processes in gene expression space to represent developing populations of cells, and we use optimal transport to recover the temporal couplings of the process. We apply these ideas to study 315,000 single-cell RNA-sequencing profiles collected at 40 time points over 18 days of reprogramming fibroblasts into induced pluripotent stem cells. To validate the optimal transport model, we demonstrate that it can accurately predict developmental states at held-out time points. We construct a high-resolution map of reprogramming that rediscovers known features; uncovers new alternative cell fates including neural- and placental-like cells; predicts the origin and fate of any cell class; and implicates regulatory models in particular trajectories. Of these findings, we highlight the transcription factor Obox6 and the paracrine signaling factor GDF9, which we experimentally show enhance reprogramming efficiency. Our approach provides a general framework for investigating cellular differentiation, and poses some interesting questions in theoretical statistics.
Bio: Geoffrey Schiebinger is a postdoctoral fellow in the MIT Center for Statistics and the Klarman Cell Observatory at the Broad Institute of MIT and Harvard. His postdoctoral mentors are Eric Lander, Aviv Regev, and Philippe Rigollet. Geoffrey has won numerous academic awards including a Career Award at the Scientific Interface from the Burroughs Welcome Fund, and a prize for Best Contribution to the conference Statistical Challenges in Single Cell Analysis organized by ETH Zurich. Before coming to MIT, Geoff studied Statistics at UC Berkeley, where he earned his Ph.D. in May 2016 for a doctoral thesis on the Mathematics of Precision Measurement. He is fortunate to have been advised by Benjamin Recht, and also work with Martin Wainwright, Bin Yu, and Aditya Guntuboyina. Geoffrey attended Stanford University from 2007 – 2011 for his undergraduate degree in mathematics with a minor in physics and master’s degree in electrical engineering.
Refreshments will be served at 3:00pm in the 3rd floor lounge of Hanes Hall