Bioassay protocol metadata annotation: Proposed standards adoption.

We present a standardized metadata template for assays used in pharmaceutical drug discovery research, according to the FAIR principles. We also describe the use of an automated tool for annotating assays from a variety of sources, including PubChem, commercial assay providers, and the peer-reviewed literature, to this metadata template. Adoption of a standardized metadata template will allow drug discovery scientists to better understand and compare the increasing amounts of assay data becoming available, and will facilitate the use of artificial intelligence tools and other computational methods for analysis and prediction.

An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome evasion via MAVS UFMylation.

Epstein-Barr virus (EBV) causes infectious mononucleosis, triggers multiple sclerosis, and is associated with 200,000 cancers/year. EBV colonizes the human B cell compartment and periodically reactivates, inducing expression of 80 viral proteins. However, much remains unknown about how EBV remodels host cells and dismantles key antiviral responses.

JUMPptm: Integrated software for sensitive identification of post-translational modifications and its application in Alzheimer's disease study.

Background: Mass spectrometry (MS)-based proteomic analysis of posttranslational modifications (PTMs) usually requires the pre-enrichment of modified proteins or peptides. However, recent ultra-deep whole proteome profiling generates millions of spectra in a single experiment, leaving many unassigned spectra, some of which may be derived from PTM peptides.

Methods: Here we present JUMPptm, an integrative computational pipeline, to extract PTMs from unenriched whole proteome.

29-Plex tandem mass tag mass spectrometry enabling accurate quantification by interference correction.

Tandem mass tag (TMT) mass spectrometry is a mainstream isobaric chemical labeling strategy for profiling proteomes. Here we present a 29-plex TMT method to combine the 11-plex and 18-plex labeling strategies. The 29-plex method was examined with a pooled sample composed of 1×, 3×, and 10× Escherichia coli peptides with 100× human background peptides, which generated two E.

Preliminary study of the contraceptive effect of a self-assembling intrauterine device (iUPODs) in mares maintained in a paddock with a fertile stallion.

There is an urgent need for practical methods of population control (i.e., contraception and/or sterilization) for free-roaming (i.

JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics.

With recent advances in mass spectrometry-based proteomics technologies, deep profiling of hundreds of proteomes has become increasingly feasible. However, deriving biological insights from such valuable datasets is challenging. Here we introduce a systems biology-based software JUMPn, and its associated protocol to organize the proteome into protein co-expression clusters across samples and protein-protein interaction (PPI) networks connected by modules (e.

Proteomic landscape of Alzheimer's Disease: novel insights into pathogenesis and biomarker discovery.

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer's disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity.

Self-reporting data assets and their representation in the pharmaceutical industry.

Standardizing data is crucial for preserving and exchanging scientific information. In particular, recording the context in which data were created ensures that information remains findable, accessible, interoperable, and reusable. Here, we introduce the concept of self-reporting data assets (SRDAs), which preserve data and contextual information.

Coming of age of Allotrope: Proceedings from the Fall 2020 Allotrope Connect.

The Allotrope Foundation (AF) is a group of pharmaceutical, device vendor, and software companies that develops and releases technologies [the Allotrope Data Format (ADF), the Allotrope Foundation Ontology (AFO), and the Allotrope Data Models (ADM)] to simplify the exchange of electronic data. We present here the first comprehensive history of the AF, its structure, a list of members and partners, and an introduction to the technologies. Finally, we provide current insights into the adoption and development of the technologies by summarizing the Fall 2020 Allotrope Connect virtual conference.

Quantifying drug tissue biodistribution by integrating high content screening with deep-learning analysis.

Quantitatively determining in vivo achievable drug concentrations in targeted organs of animal models and subsequent target engagement confirmation is a challenge to drug discovery and translation due to lack of bioassay technologies that can discriminate drug binding with different mechanisms. We have developed a multiplexed and high-throughput method to quantify drug distribution in tissues by integrating high content screening (HCS) with U-Net based deep learning (DL) image analysis models. This technology combination allowed direct visualization and quantification of biologics drug binding in targeted tissues with cellular resolution, thus enabling biologists to objectively determine drug binding kinetics.

Effect of Chronic Administration of Oxytocin on Corpus Luteum Function in Cycling Mares.

The objective of this study was to determine if intramuscular administration of 60 units of oxytocin once daily for 29 days, regardless of when treatment was initiated during the estrous cycle (i.e., without monitoring estrous behavior and/or detecting ovulation), would induce prolonged corpus luteum (CL) function in cycling mares.

Evaluation of a Proprietary Slow-Release Oxytocin Formulation on Corpus Luteum Function in Mares.

Prolonging function of the corpus luteum (CL) is a method of suppressing estrus that relies on continued secretion of endogenous progesterone to keep mares out of heat naturally. The use of oxytocin treatment to prolong CL function is gaining increasing use, and the most common treatment protocol involves administration of 60 units of oxytocin intramuscularly (IM) once daily on days 7-14 after ovulation (eight daily treatments). Although that protocol induces prolonged CL function in ≥70% of treated mares, the need for daily administration is a drawback to its use.

Expression profiles of select genes in cumulus-oocyte complexes from young and aged mares.

There is compelling evidence that oocytes from mares >18 years of age have a high incidence of inherent defects that result in early embryonic loss. In women, an age-related decrease in oocyte quality is associated with an increased incidence of aneuploidy and it has recently been determined that the gene expression profile of human oocytes is altered with advancing age. We hypothesised that similar age-related aberrations in gene expression occur in equine oocytes.

Molecular clinical safety intelligence: a system for bridging clinically focused safety knowledge to early-stage drug discovery - the GSK experience.

Drug toxicity is a major cause of late-stage product attrition. During lead identification and optimization phases little information is typically available about which molecules might have safety concerns. A system was built linking chemistry, preclinical and human safety information, enabling scientists to lever safety knowledge across multiple disciplines.

Disclosing ambiguous gene aliases by automatic literature profiling.

Background: Retrieving pertinent information from biological scientific literature requires cutting-edge text mining methods which may be able to recognize the meaning of the very ambiguous names of biological entities. Aliases of a gene share a common vocabulary in their respective collections of PubMed abstracts. This may be true even when these aliases are not associated with the same subset of documents.

Thousands of chemical starting points for antimalarial lead identification.

Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P.

Functional antagonism of IL-1alpha induced gene expression profiles define the cAMP/PKA pathway as a unique regulator of IL-1alpha signaling networks.

Interleukin-1 (IL-1alpha) induced inflammatory and pro-fibrotic responses in human lung fibroblasts are mediated by activation of MAPK and NFkappaB pathways. The purpose of the present study was to broadly profile the activity of a variety of compounds which function as inhibitors of these key signaling pathways that may affect IL-1alpha mediated gene changes. A reference set of genes was derived from microarray analysis of IL-1alpha stimulated cells.

Parental genomes mix in mule and human cell nuclei.

Whether chromosome sets inherited from father and mother occupy separate spaces in the cell nucleus is a question first asked over 110 years ago. Recently, the nuclear organization of the genome has come increasingly into focus as an important level of epigenetic regulation. In this context, it is indispensable to know whether or not parental genomes are spatially separated.