"Super Gene Set" Causal Relationship Discovery from Functional Genomics Data

In this article, we present a computational framework to identify "causal relationships" among super gene sets. For "causal relationships," we refer to both stimulatory and inhibitory regulatory relationships, regardless of through direct or indirect mechanisms. For super gene sets, we refer to "pathways, annotated lists, and gene signatures," or PAGs. To identify causal relationships among PAGs, we extend the previous work on identifying PAG-to-PAG regulatory relationships by further requiring them to be significantly enriched with gene-to-gene co-expression pairs across the two PAGs involved. This is achieved by developing a quantitative metric based on PAG-to-PAG Co-expressions (PPC), which we use to infer the likelihood that PAG-to-PAG relationships under examination are causal-either stimulatory or inhibitory. Since true causal relationships are unknown, we approximate the overall performance of inferring causal relationships with the performance of recalling known r-type PAG-to-PAG relationships from causal PAG-to-PAG inference, using a functional genomics benchmark dataset from the GEO database. We report the area-under-curve (AUC) performance for both precision and recall being 0.81. By applying our framework to a myeloid-derived suppressor cells (MDSC) dataset, we further demonstrate that this framework is effective in helping build multi-scale biomolecular systems models with new insights on regulatory and causal links for downstream biological interpretations

Selectively decentralized reinforcement learning

Indiana University-Purdue University Indianapolis (IUPUI)The main contributions in this thesis include the selectively decentralized method in solving multi-agent reinforcement learning problems and the discretized Markov-decision-process (MDP) algorithm to compute the sub-optimal learning policy in completely unknown learning and control problems. These contributions tackle several challenges in multi-agent reinforcement learning: the unknown and dynamic nature of the learning environment, the difficulty in computing the closed-form solution of the learning problem, the slow learning performance in large-scale systems, and the questions of how/when/to whom the learning agents should communicate among themselves. Through this thesis, the selectively decentralized method, which evaluates all of the possible communicative strategies, not only increases the learning speed, achieves better learning goals but also could learn the communicative policy for each learning agent. Compared to the other state-of-the-art approaches, this thesis’s contributions offer two advantages. First, the selectively decentralized method could incorporate a wide range of well-known algorithms, including the discretized MDP, in single-agent reinforcement learning; meanwhile, the state-of-the-art approaches usually could be applied for one class of algorithms. Second, the discretized MDP algorithm could compute the sub-optimal learning policy when the environment is described in general nonlinear format; meanwhile, the other state-of-the-art approaches often assume that the environment is in limited format, particularly in feedback-linearization form. This thesis also discusses several alternative approaches for multi-agent learning, including Multidisciplinary Optimization. In addition, this thesis shows how the selectively decentralized method could successfully solve several real-worlds problems, particularly in mechanical and biological systems