TITLE: "XIST controls X chromosome dampening and autosomal genes in early human development" ABSTRACT: Female human pre-implantation embryos and naïve human pluripotent stem cells (hPSCs) equalize X-linked gene expression with males via X-chromosome dampening (XCD), a unique strategy of dosage compensation in mammals. The mechanisms controlling XCD are unknown. Here, we show that the long non-coding RNA XIST, which mediates X-chromosome inactivation (XCI), is required for XCD. XIST employs similar principles and protein partners, including SPEN, to execute XCD and XCI,…

TITLE: "Fast estimation of genetic correlation for Biobank-scale data" ABSTRACT: Genetic correlation is an important parameter in understanding the shared genetic basis across pairs of complex traits with applications ranging across disease subtyping, genetic prediction, and causal inference. The availability of genome-wide genetic data has led to a number of methods that aim to estimate genetic correlation. Methods that analyze individual genotype data (typically using a bi-variate linear mixed model) are computationally expensive to be applied to large-scale datasets such as…

TITLE: "Determining mRNA nuclear export kinetics reveals a wide range of values associated with innate immune response genes" ABSTRACT: The abundance and stimulus-responsiveness of mature mRNA is considered determined by nuclear synthesis and cytoplasmic decay. However, pre-mRNA processing and transport may also contribute, but have rarely been measured. We generated high spatio-temporal resolution RNA-seq data and developed a mathematical modeling workflow to infer kinetic parameters. We found that the effective chromatin-to-cytoplasm transport rate is gene-specific, varying 100-fold. Importantly, effective export…

TITLE: "Oncogenic alterations in the p53 pathway abolish oscillatory competence" ABSTRACT: The tumor suppressor p53 displays concentration oscillations in response to DNA damage, a behavior that has been suggested to be essential to its anti-cancer function.  Many genetic alterations in the p53 pathway have been shown to be oncogenic, whether by experiment or by clinical associations with various cancers. These oncogenic alterations include somatic mutations, copy number variations and inherited polymorphisms. Using a differential equation model of p53-Mdm2 dynamics, we employ…

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TITLE: "Learning Sparse Representation of Single Cells using Projective Nonnegative Matrix Factorization (pNMF)"

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TITLE: "Linking exposure dose to infectious disease development using mechanistic models" (using SARS-CoV-2 in a mouse model as an illustration) ABSTRACT: Disease development after exposure to a pathogen does not follow a yes/no process, but rather a spectrum of disease manifestations influenced by host, pathogen and environmental factors. In particular, exposure dose can impact incubation time, shedding intensity and disease severity. However, classical dose-response models only consider the probability of disease development, neglecting the diversity of disease manifestations. In contrast, more…