An integrative ENCODE resource for cancer genomics.

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types.

RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework.

Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair.

Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin.

Interpreting Reverse Transcriptase Termination and Mutation Events for Greater Insight into the Chemical Probing of RNA.

Chemical probing has the power to provide insight into RNA conformation in vivo and in vitro, but interpreting the results depends on methods to detect the chemically modified nucleotides. Traditionally, the presence of modified bases was inferred from their ability to halt reverse transcriptase during primer extension and the locations of termination sites observed by electrophoresis or sequencing. More recently, modification-induced mutations have been used as a readout for chemical probing data.

The Properties of Long Noncoding RNAs That Regulate Chromatin.

Beyond coding for proteins, RNA molecules have well-established functions in the posttranscriptional regulation of gene expression. Less clear are the upstream roles of RNA in regulating transcription and chromatin-based processes in the nucleus. RNA is transcribed in the nucleus, so it is logical that RNA could play diverse and broad roles that would impact human physiology.

Probing Xist RNA Structure in Cells Using Targeted Structure-Seq.

The long non-coding RNA (lncRNA) Xist is a master regulator of X-chromosome inactivation in mammalian cells. Models for how Xist and other lncRNAs function depend on thermodynamically stable secondary and higher-order structures that RNAs can form in the context of a cell. Probing accessible RNA bases can provide data to build models of RNA conformation that provide insight into RNA function, molecular evolution, and modularity.

Tracking Distinct RNA Populations Using Efficient and Reversible Covalent Chemistry.

We describe a chemical method to label and purify 4-thiouridine (s(4)U)-containing RNA. We demonstrate that methanethiosulfonate (MTS) reagents form disulfide bonds with s(4)U more efficiently than the commonly used HPDP-biotin, leading to higher yields and less biased enrichment. This increase in efficiency allowed us to use s(4)U labeling to study global microRNA (miRNA) turnover in proliferating cultured human cells without perturbing global miRNA levels or the miRNA processing machinery.

Comparative analysis of pseudogenes across three phyla.

Pseudogenes are degraded fossil copies of genes. Here, we report a comparison of pseudogenes spanning three phyla, leveraging the completed annotations of the human, worm, and fly genomes, which we make available as an online resource. We find that pseudogenes are lineage specific, much more so than protein-coding genes, reflecting the different remodeling processes marking each organism's genome evolution.

The structural diversity of ABS₃ compounds with d⁰ electronic configuration for the B-cation.

We use first-principles density functional theory within the local density approximation to ascertain the ground state structure of real and theoretical compounds with the formula ABS3 (A = K, Rb, Cs, Ca, Sr, Ba, Tl, Sn, Pb, and Bi; and B = Sc, Y, Ti, Zr, V, and Nb) under the constraint that B must have a d(0) electronic configuration. Our findings indicate that none of these AB combinations prefer a perovskite ground state with corner-sharing BS6 octahedra, but that they prefer phases with either edge- or face-sharing motifs. Further, a simple two-dimensional structure field map created from A and B ionic radii provides a neat demarcation between combinations preferring face-sharing versus edge-sharing phases for most of these combinations.

High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation.

The Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes. During XCI, Xist coats the future inactive X chromosome (Xi) and recruits Polycomb repressive complex 2 (PRC2) to the X-inactivation centre (Xic). How Xist spreads silencing on a 150-megabases scale is unclear.

Polarization dependence of palladium deposition on ferroelectric lithium niobate (0001) surfaces.

We investigate the effect of ferroelectric polarization direction on the geometric properties of Pd deposited on the positive and negative surfaces of LiNbO(3) (0001). We predict preferred geometries and diffusion properties of small Pd clusters using density functional theory, and use these calculations as the basis for kinetic Monte Carlo simulations of Pd deposition on a larger scale. Our results show that on the positive surface, Pd atoms favor a clustered configuration, while on the negative surface, Pd atoms are adsorbed in a more dispersed pattern due to suppression of diffusion and agglomeration.

MET receptor sequence variants R970C and T992I lack transforming capacity.

High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant "passenger" mutations remains a major challenge. Here we present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I). Previous reports indicated that these sequence variants are transforming and contribute to oncogenesis.