Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into consideration hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster. Findr is publicly available at https://github.com/lingfeiwang/findr.

Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded protein response (UPR), which can promote recovery of ER proteostasis and cell survival or trigger programmed cell death. Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional states associated with the adaptive versus terminal UPR in the mouse intestinal epithelium. We integrated these transcriptional programs with genome-scale CRISPR screening to dissect the UPR pathway functionally. We identified QRICH1 as a key effector of the PERK-eIF2α axis of the UPR. QRICH1 controlled a transcriptional program associated with translation and secretory networks that were specifically up-regulated in inflammatory pathologies. Thus, QRICH1 dictates cell fate in response to pathological ER stress.

We introduce a string-inspired model for a bouncing/cyclic universe, utilizing the scalar-tachyon coupling as well as contribution from curvature in a closed universe. The universe undergoes the locked inflation, tachyon matter dominated rolling expansion, turnaround and contraction, as well as the subsequent deflation and "bounce" in each cycle of the cosmological evolution. We perform extensive analytic and numerical studies of the above evolution process.The minimum size of the universe is nonzero for generic initial values. The smooth bounce are made possible because of the negative contribution to effective energy density by the curvature term. No ghosts are ever generated at any point in the entire evolution of the universe, with the Null, Weak, and Dominant Energy Conditions preserved even at the bounce points, contrary to many bounce models previously proposed. And the Strong Energy Condition is satisfied in periods with tachyon matter domination.