Information content differentiates enhancers from silencers in mouse photoreceptors

Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.

Maternal Obesity Dysregulates Fetal Hematopoietic Stem and Progenitor Cell Development in Rhesus Macaques

ABSTRACTInfants from obese moms have an increased susceptibility to immune dysregulation. However, the mechanisms by which maternal obesity alters fetal hematopoiesis remain largely unknown. Here, we determined the impact of maternal consumption of an obesogenic western-style diet (WSD) on hematopoietic development in fetal rhesus macaques using a combination of phenotypic, functional, and genomic assays. We demonstrate that maternal WSD resulted in accelerated fetal growth and altered fetal hematopoiesis. Specifically, single-cell RNA sequencing analysis of fetal bone marrow HSPCs showed that maternal WSD altered the transcriptional program of the common lymphoid progenitors and decreased the frequencies of bone marrow B-cells and NK-cells. Despite an expansion of monocyte progenitors in FBM, fetal blood monocytes from the WSD group demonstrated a blunted response to bacterial lipopolysaccharide. Furthermore, maternal WSD led to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ-/-mice. Collectively, this study demonstrates that maternal WSD dysregulates fetal HSPC development.

Biomedical Computational Linguistics and Natural Language Processing

Computational linguistics has its origins in the post-Second World War research on translation of Russian-language scientific journal articles in the United States. Today, biomedical natural language processing treats clinical data, the scientific literature, and social media, with use cases ranging from studying adverse effects of drugs to interpreting high-throughput genomic assays (Névéol and Zweigenbaum 2018). Many of the most prominent research areas in the field involve extracting information from text and normalizing it to enormous databases of domain-relevant semantic classes, such as genes, diseases, and biological processes. Moving forward, the field is expected to play a significant role in understanding reproducibility in natural language processing.

Genomic Assays in Node Positive Breast Cancer Patients: A Review

In recent years, developments in breast cancer have allowed yet another realization of individualized medicine in the field of oncology. One of these advances is genomic assays, which are considered elements of standard clinical practice in the management of breast cancer. These assays are widely used today not only to measure recurrence risk in breast cancer patients at an early stage but also to tailor treatment as well and minimize avoidable treatment side effects. At present, genomic tests are applied extensively in node negative disease. In this article, we review the use of these tests in node positive disease, explore their ramifications on neoadjuvant chemotherapy decisions, highlight sufficiently powered recent studies emphasizing their use and review the most recent guidelines.

Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors

Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.