Learning Generative Causal Models from Sparse Temporal Observations during Cellular Reprogramming


Project Description

​Recent work on stem cells and different mature specialized cells in different systems/organs (neurons, blood cells,) has revealed a stunning plasticity and capacity of reprogramming cells. For example, mature cells can be reprogrammed into pluripotent stem cells, and exciting work on engineered design of tissues and organs (organoids) are underway. On the one hand the community has since the sequencing of the human genome produced very efficient tools to read off the corresponding molecular events accompanying reprogramming and engineering of cells. Recently, the discovery of the CRISPR techniques has equipped us with unprecedented opportunities for precise writing or editing of the genomes. These developments in fundamental biology and biotechnology are currently opening new tools and perspectives of vital significance for drug development, regenerative medicine, synthetic biology, and personalized medicine. Yet, in essence all these efforts require and would be greatly facilitated if we could advance from correlative data-analysis to a predictive discovery of which interventions (edits, engineering) are producing which effects. Thus, we are facing the fundamental problem on how to discover causal relations from data, or in other words, can we derive quantitative predictive laws fromdata?We offer internships forseveral highly motivatedbachelor (B.Sc.) ormaster (M.Sc.) students who will explore this fundamental question primarily from a computational standpoint. This includes using high-performance simulations of dynamical models, and design of algorithms in a controlled in-silico environment. For example, to identify (a) efficient algorithms for generation of ensembles of dynamical models, (b) use supervised deep learning algorithms for pattern discovery in large-scale simulation data-sets, (c) to perform deep data-driven analysis of computational models in biology, (d) pursue investigations of transfer entropy and related techniques for system identification. These tools will be tested utilizing rich and recent molecular data on cellular reprogramming.​​ ​​​​
Program - BioScience
Division - Biological and Environmental Sciences and Engineering
Field of Study - ​computer science, mathematical modeling, machine learning, systems biology, bioscience

About the

Jesper Tegner

Jesper Tegner

Desired Project Deliverables

​Individual projects will be tailored and narrowly designed from the above palette according to interest of the student, technical proficiency, and level of study. The project is suitable for candidates fascinated by dynamical causal systems, be it computational or those we find in the natural world, i.e. living cells. We expect you (a) to bring enthusiasm, creativity, and hard work, (b) give lab seminars on your work, and (c) produce a final written report.In returnthis facilitates your critical thinking, presentations skills, and scientific writing.Yourresearch, in collaboration and with support of team members, may lead to scientific publications. We publish avidly in both bioscience and computational sciences, not for the fame but rather as steps aiming to and motivated both by our quest of asking fundamental questions of relevance to human nature and discovery of transformative intelligent technologies inspired from nature. You will get a good hands-on perspective on the frontiers in dynamical systems and bioscience using state-of-the-art simulation and machine learning tools.