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Differentiation alters molecular properties of stem and progenitor cells, leading to changing shape and movement characteristics. We present a deep neural network that prospectively predicts lineage choice in differentiating primary hematopoietic progenitors, using image patches from brightfield microscopy and cellular movement. Surprisingly, lineage choice can be detected up to three generations before conventional molecular markers are observable. Our approach allows identifying cells with differentially expressed lineage-specifying genes without molecular labeling.

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence sub-optimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a non-parametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a several fold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package *

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Reinforcement learning agents can include different components, such as policies, value functions, state representations, and environment models. Any or all of these can be the loci of knowledge, i.e., structures where knowledge, whether given or learned, can be deposited and reused. The objective of an agent is to behave so as to maximise the sum of a suitable scalar function of state: the reward. As far as the learning algorithm is concerned, these rewards are typically given and immutable. In this paper we instead consider the proposition that the reward function itself may be a good locus of knowledge. This is consistent with a common use, in the literature, of hand-designed intrinsic rewards to improve the learning dynamics of an agent. We adopt the multi-lifetime setting of the Optimal Rewards Framework, and propose to meta-learn an intrinsic reward function from experience that allows agents to maximise their extrinsic rewards accumulated until the end of their lifetimes. Rewards as a locus of knowledge provide guidance on "what" the agent should strive to do rather than "how" the agent should behave; the latter is more directly captured in policies or value functions for example. Thus, our focus here is on demonstrating the following: (1) that it is feasible to meta-learn good reward functions, (2) that the learned reward functions can capture interesting kinds of "what" knowledge, and (3) that because of the indirectness of this form of knowledge the learned reward functions can generalise to other kinds of agents and to changes in the dynamics of the environment. * Equal contribution. † Work done during an internship at DeepMind.