RegPrecise web services interface: programmatic access to the transcriptional regulatory interactions in bacteria reconstructed by comparative genomics.

Web services application programming interface (API) was developed to provide a programmatic access to the regulatory interactions accumulated in the RegPrecise database (http://regprecise.lbl.gov), a core resource on transcriptional regulation for the microbial domain of the Department of Energy (DOE) Systems Biology Knowledgebase. RegPrecise captures and visualize regulogs, sets of genes controlled by orthologous regulators in several closely related bacterial genomes, that were reconstructed by comparative genomics. The current release of RegPrecise 2.0 includes >1400 regulogs controlled either by protein transcription factors or by conserved ribonucleic acid regulatory motifs in >250 genomes from 24 taxonomic groups of bacteria. The reference regulons accumulated in RegPrecise can serve as a basis for automatic annotation of regulatory interactions in newly sequenced genomes. The developed API provides an efficient access to the RegPrecise data by a comprehensive set of 14 web service resources. The RegPrecise web services API is freely accessible at http://regprecise.lbl.gov/RegPrecise/services.jsp with no login requirements

Role of Acetylcholinesterase in β-Amyloid Aggregation Studied by Accelerated Molecular Dynamics

© 2016, Springer Science+Business Media New York.Mechanisms of Alzheimer’s disease development are still under investigation. It was shown that acetylcholinesterase promotes aggregation of β-amyloid. Accelerated molecular dynamics simulations were performed to investigate molecular mechanisms of this process. Results showed that Aβ is strongly attracted to the surface of acetylcholinesterase and forms stable complexes. It was hypothesized that acetylcholinesterase serves as a nucleation center for propagation of β-amyloid aggregation

Improving the framework for assessment of ecological change in the Arctic: A circumpolar synthesis of freshwater biodiversity

1. Climate warming and subsequent landscape transformations result in rapid ecological change in Arctic freshwaters. Here we provide a synthesis of the diversity of benthic diatoms, plankton, macrophytes, macroinvertebrates, and fish in Arctic freshwaters.2. We developed a multi-organism measure of alpha diversity to characterise circumpolar spatial patterns and their environmental correlates, and we assessed ecoregion-level beta diversity for all organism groups across the Arctic.3. Alpha diversity was lowest at high latitudes and elevations and where dispersal barriers exist. Diversity was positively related to temperature, and both temperature and connectivity limited diversity on high latitude islands. Beta diversity was highly variable among ecoregions for most organism groups, ranging from 0 (complete similarity) to 1 (complete dissimilarity). The high degree of dissimilarity within many ecoregions illustrates the uniqueness of many Arctic freshwater communities.4. Northward range expansion of freshwater taxa into Arctic regions may lead to increased competition for cold-stenothermic and cold-adapted species, and ultimately lead to the extinction of unique Arctic species. Societal responses to predicted impacts include: (1) actions to improve detection of changes (e.g., harmonised monitoring, remote sensing) and engagement with Arctic residents and Indigenous Peoples; and (2) actions to reduce the impact of unwanted changes (e.g., reductions of CO2 emissions, action against the spread of invasive species).5. Current Arctic freshwater monitoring shows large gaps in spatial coverage, while time series data are scarce. Arctic countries should develop an intensified, long-term monitoring programme with routine reporting. Such an approach will allow detection of long-term changes in water quality, biodiversity, and ecosystem services of Arctic freshwaters

RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov

BTK, NuTM2A, and PRPF19 are Novel KMT2A Partner Genes in Childhood Acute Leukemia

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients’ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subse-quent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: KMT2A rearrangement assessment was supported by the Russian Science Foundation (grant no. 19-75-10056). Quantitative RT-PCR for MRD monitoring was supported by Russian Presidential (grant no. MK-1645.2020.7)

First circumpolar assessment of Arctic freshwater phytoplankton and zooplankton diversity : Spatial patterns and environmental factors

Arctic freshwaters are facing multiple environmental pressures, including rapid climate change and increasing land-use activities. Freshwater plankton assemblages are expected to reflect the effects of these stressors through shifts in species distributions and changes to biodiversity. These changes may occur rapidly due to the short generation times and high dispersal capabilities of both phyto- and zooplankton. Spatial patterns and contemporary trends in plankton diversity throughout the circumpolar region were assessed using data from more than 300 lakes in the U.S.A. (Alaska), Canada, Greenland, Iceland, the Faroe Islands, Norway, Sweden, Finland, and Russia. The main objectives of this study were: (1) to assess spatial patterns of plankton diversity focusing on pelagic communities; (2) to assess dominant component of beta diversity (turnover or nestedness); (3) to identify which environmental factors best explain diversity; and (4) to provide recommendations for future monitoring and assessment of freshwater plankton communities across the Arctic region. Phytoplankton and crustacean zooplankton diversity varied substantially across the Arctic and was positively related to summer air temperature. However, for zooplankton, the positive correlation between summer temperature and species numbers decreased with increasing latitude. Taxonomic richness was lower in the high Arctic compared to the sub- and low Arctic for zooplankton but this pattern was less clear for phytoplankton. Fennoscandia and inland regions of Russia represented hotspots for, respectively, phytoplankton and zooplankton diversity, whereas isolated regions had lower taxonomic richness. Ecoregions with high alpha diversity generally also had high beta diversity, and turnover was the most important component of beta diversity in all ecoregions. For both phytoplankton and zooplankton, climatic variables were the most important environmental factors influencing diversity patterns, consistent with previous studies that examined shorter temperature gradients. However, barriers to dispersal may have also played a role in limiting diversity on islands. A better understanding of how diversity patterns are determined by colonisation history, environmental variables, and biotic interactions requires more monitoring data with locations dispersed evenly across the circumpolar Arctic. Furthermore, the importance of turnover in regional diversity patterns indicates that more extensive sampling is required to fully characterise the species pool of Arctic lakes.Peer reviewe

Exploratory Study of the Long-Term Persistence of <i>Yersinia pestis</i> in the Cells of Soil-Inhabiting Ameba - <i>Acanthamoeba Sp.</i>

Objective of the study is to explore the feasibility of the long-term persistence of Yersinia pestis strains in association with ameba - Acanthamoeba sp. Materials and methods. Investigated has been interaction of ameba - Acanthamoeba sp., isolated from rodent burrows in the Pre-Caspian sandy, Volga-Ural steppe, and Pre-Caspian North-Western steppe natural foci, with 4 strains of Y. pestis of the main subspecies, 1 strain of caucasica and 1 strain of altai subspecies. Results and discussion. It is established that the strains of the main subspecies survive in the cells of ameba at 26 °C and 20 % humidity (modeling of the drought conditions in the natural plague foci) within 2-4 months of experiment, and 10-20 times longer that in pure culture. Two strains of the non-main ssp. have not demonstrated an increase in persistency in association with Acanthamoeba sp., which may occur due to degraded resistance to phagocytosis in the ameba of this specie. Using fluorescent and transmission electronic microscopy, it is determined that the cells of plague agent persist in ameba cells in individual vacuoles, enclosed in endoplasmic reticulum. The data obtained may testify to the possible involvement of ameba Acanthamoeba sp. . into sustainment of Y. pestis in soil biocoenoses of natural plague foci

RegPrecise: a database of curated genomic inferences of transcriptional regulatory interactions in prokaryotes

The RegPrecise database (http://regprecise.lbl.gov) was developed for capturing, visualization and analysis of predicted transcription factor regulons in prokaryotes that were reconstructed and manually curated by utilizing the comparative genomic approach. A significant number of high-quality inferences of transcriptional regulatory interactions have been already accumulated for diverse taxonomic groups of bacteria. The reconstructed regulons include transcription factors, their cognate DNA motifs and regulated genes/operons linked to the candidate transcription factor binding sites. The RegPrecise allows for browsing the regulon collections for: (i) conservation of DNA binding sites and regulated genes for a particular regulon across diverse taxonomic lineages; (ii) sets of regulons for a family of transcription factors; (iii) repertoire of regulons in a particular taxonomic group of species; (iv) regulons associated with a metabolic pathway or a biological process in various genomes. The initial release of the database includes ∼11 500 candidate binding sites for ∼400 orthologous groups of transcription factors from over 350 prokaryotic genomes. Majority of these data are represented by genome-wide regulon reconstructions in Shewanella and Streptococcus genera and a large-scale prediction of regulons for the LacI family of transcription factors. Another section in the database represents the results of accurate regulon propagation to the closely related genomes

An environment for relation mining over richly annotated corpora: the case of GENIA

BACKGROUND: The biomedical domain is witnessing a rapid growth of the amount of published scientific results, which makes it increasingly difficult to filter the core information. There is a real need for support tools that 'digest' the published results and extract the most important information. RESULTS: We describe and evaluate an environment supporting the extraction of domain-specific relations, such as protein-protein interactions, from a richly-annotated corpus. We use full, deep-linguistic parsing and manually created, versatile patterns, expressing a large set of syntactic alternations, plus semantic ontology information. CONCLUSION: The experiments show that our approach described is capable of delivering high-precision results, while maintaining sufficient levels of recall. The high level of abstraction of the rules used by the system, which are considerably more powerful and versatile than finite-state approaches, allows speedy interactive development and validation

Corpus annotation for mining biomedical events from literature

<p>Abstract</p> <p>Background</p> <p>Advanced Text Mining (TM) such as semantic enrichment of papers, event or relation extraction, and intelligent Question Answering have increasingly attracted attention in the bio-medical domain. For such attempts to succeed, text annotation from the biological point of view is indispensable. However, due to the complexity of the task, semantic annotation has never been tried on a large scale, apart from relatively simple term annotation.</p> <p>Results</p> <p>We have completed a new type of semantic annotation, event annotation, which is an addition to the existing annotations in the GENIA corpus. The corpus has already been annotated with POS (Parts of Speech), syntactic trees, terms, etc. The new annotation was made on half of the GENIA corpus, consisting of 1,000 Medline abstracts. It contains 9,372 sentences in which 36,114 events are identified. The major challenges during event annotation were (1) to design a scheme of annotation which meets specific requirements of text annotation, (2) to achieve biology-oriented annotation which reflect biologists' interpretation of text, and (3) to ensure the homogeneity of annotation quality across annotators. To meet these challenges, we introduced new concepts such as Single-facet Annotation and Semantic Typing, which have collectively contributed to successful completion of a large scale annotation.</p> <p>Conclusion</p> <p>The resulting event-annotated corpus is the largest and one of the best in quality among similar annotation efforts. We expect it to become a valuable resource for NLP (Natural Language Processing)-based TM in the bio-medical domain.</p