Spatial clustering and common regulatory elements correlate with coordinated gene expression

Many cellular responses to surrounding cues require temporally concerted transcriptional regulation of multiple genes. In prokaryotic cells, a single-input-module motif with one transcription factor regulating multiple target genes can generate coordinated gene expression. In eukaryotic cells, transcriptional activity of a gene is affected by not only transcription factors but also the epigenetic modifications and three-dimensional chromosome structure of the gene. To examine how local gene environment and transcription factor regulation are coupled, we performed a combined analysis of time-course RNA-seq data of TGF-\b{eta} treated MCF10A cells and related epigenomic and Hi-C data. Using Dynamic Regulatory Events Miner (DREM), we clustered differentially expressed genes based on gene expression profiles and associated transcription factors. Genes in each class have similar temporal gene expression patterns and share common transcription factors. Next, we defined a set of linear and radial distribution functions, as used in statistical physics, to measure the distributions of genes within a class both spatially and linearly along the genomic sequence. Remarkably, genes within the same class despite sometimes being separated by tens of million bases (Mb) along genomic sequence show a significantly higher tendency to be spatially close despite sometimes being separated by tens of Mb along the genomic sequence than those belonging to different classes do. Analyses extended to the process of mouse nervous system development arrived at similar conclusions. Future studies will be able to test whether this spatial organization of chromosomes contributes to concerted gene expression.Comment: 30 pages, 9 figures, accepted in PLoS Computational Biolog

A Numerical Approach to Solving an Inverse Heat Conduction Problem Using the Levenberg-Marquardt Algorithm

This chapter is intended to provide a numerical algorithm involving the combined use of the Levenberg-Marquardt algorithm and the Galerkin finite element method for estimating the diffusion coefficient in an inverse heat conduction problem (IHCP). In the present study, the functional form of the diffusion coefficient is an unknown priori. The unknown diffusion coefficient is approximated by the polynomial form and the present numerical algorithm is employed to find the solution. Numerical experiments are presented to show the efficiency of the proposed method

Careful at Estimation and Bold at Exploration

Exploration strategies in continuous action space are often heuristic due to the infinite actions, and these kinds of methods cannot derive a general conclusion. In prior work, it has been shown that policy-based exploration is beneficial for continuous action space in deterministic policy reinforcement learning(DPRL). However, policy-based exploration in DPRL has two prominent issues: aimless exploration and policy divergence, and the policy gradient for exploration is only sometimes helpful due to inaccurate estimation. Based on the double-Q function framework, we introduce a novel exploration strategy to mitigate these issues, separate from the policy gradient. We first propose the greedy Q softmax update schema for Q value update. The expected Q value is derived by weighted summing the conservative Q value over actions, and the weight is the corresponding greedy Q value. Greedy Q takes the maximum value of the two Q functions, and conservative Q takes the minimum value of the two different Q functions. For practicality, this theoretical basis is then extended to allow us to combine action exploration with the Q value update, except for the premise that we have a surrogate policy that behaves like this exploration policy. In practice, we construct such an exploration policy with a few sampled actions, and to meet the premise, we learn such a surrogate policy by minimizing the KL divergence between the target policy and the exploration policy constructed by the conservative Q. We evaluate our method on the Mujoco benchmark and demonstrate superior performance compared to previous state-of-the-art methods across various environments, particularly in the most complex Humanoid environment.Comment: 20 page