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At least 253 records · Page 14Linked to original sources

Evolution of matrix and bone gamma-carboxyglutamic acid proteins in vertebrates.

The evolution of calcified tissues is a defining feature in vertebrate evolution. Investigating the evolution of proteins involved in tissue calcification should help elucidate how calcified tissues have evolved. The purpose of this study was to collect and compare sequences of matrix and bone gamma-carboxyglutamic acid proteins (MGP and BGP, respectively) to identify common features and determine the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were cloned using standard methods or reconstructed through the use of comparative genomics and data mining. These sequences were compared with available annotated sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20 MGPs) have been identified across 32 different species (representing most classes of vertebrates), and evolutionarily conserved features in both MGP and BGP were analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that: 1) MGP and BGP genes originated from two genome duplications that occurred around 500 and 400 million years ago before jawless and jawed fish evolved, respectively; 2) MGP appeared first concomitantly with the emergence of cartilaginous structures, and BGP appeared thereafter along with bony structures; and 3) BGP derives from MGP. We also propose a highly specific pattern definition for the Gla domain of BGP and MGP.

Amino Acid Sequence↗

Dragon Plant Biology Explorer. A text-mining tool for integrating associations between genetic and biochemical entities with genome annotation and biochemical terms lists.

We introduce a tool for text mining, Dragon Plant Biology Explorer (DPBE) that integrates information on Arabidopsis (Arabidopsis thaliana) genes with their functions, based on gene ontologies and biochemical entity vocabularies, and presents the associations as interactive networks. The associations are based on (1) user-provided PubMed abstracts; (2) a list of Arabidopsis genes compiled by The Arabidopsis Information Resource; (3) user-defined combinations of four vocabulary lists based on the ones developed by the general, plant, and Arabidopsis GO consortia; and (4) three lists developed here based on metabolic pathways, enzymes, and metabolites derived from AraCyc, BRENDA, and other metabolism databases. We demonstrate how various combinations can be applied to fields of (1) gene function and gene interaction analyses, (2) plant development, (3) biochemistry and metabolism, and (4) pharmacology of bioactive compounds. Furthermore, we show the suitability of DPBE for systems approaches by integration with "omics" platform outputs. Using a list of abiotic stress-related genes identified by microarray experiments, we show how this tool can be used to rapidly build an information base on the previously reported relationships. This tool complements the existing biological resources for systems biology by identifying potentially novel associations using text analysis between cellular entities based on genome annotation terms. Thus, it allows researchers to efficiently summarize existing information for a group of genes or pathways, so as to make better informed choices for designing validation experiments. Last, DPBE can be helpful for beginning researchers and graduate students to summarize vast information in an unfamiliar area. DPBE is freely available for academic and nonprofit users at http://research.i2r.a-star.edu.sg/DRAGON/ME2/.

Arabidopsis↗

Bioinformatic analysis of neuropeptide and receptor expression profiles during midgut metamorphosis in Drosophila melanogaster.

Neuropeptides are important messenger molecules in invertebrates, serving as neuromodulators in the nervous system and as regulatory hormones released into the circulation. Understanding the function of neuropeptides will require the integration of genetic, biochemical, physiological and behavioral information. The advent of DNA microarrays and bioinformatic databases provides a wealth of data describing the expression profiles of thousands of genes during biological processes. One such array catalogs the developmental patterns of gene expression during the metamorphic transformation of the Drosophila midgut. We have mined the data from this experiment to explore changes of expression in genes coding for known neuropeptides, peptide hormones, and their receptors during the metamorphosis of the midgut. We found small but significant changes in the expression of the peptides diuretic hormone, FGLa-type allatostatins, myoinhibiting peptide, ecdysis-triggering hormone, drosokinin and the burs subunit of bursicon, as well as the receptors DAR-2, NPFR1, ALCR-2, Lkr and DH-R. Just as advances have been made in understanding the molecular basis of invertebrate neuropeptide action by analysis of genome projects, data mining of gene expression databases can help to integrate molecular, biochemical and physiological knowledge of biological processes.

Animals↗

Novel immunoglobulin-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM or ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44.

Members of the immunoglobulin superfamily (IgSF) include a group of innate immune receptors located in the leukocyte receptor complex (LRC) and other small clusters such as the TREM/NKp44 cluster. These receptors are characterised by the presence of immunoglobulin domains, a stalk, a transmembrane domain, and a cytoplasmic region containing either an immunoreceptor tyrosine-based inhibitory motif (ITIM) or are linked to an adapter molecule with an activation motif (ITAM) for downstream signalling. We have isolated two carp cDNA sequences encoding receptors in which the extracellular Ig domain structurally resembles the novel V-type Ig domain of NKp44. This is supported by a homology model. The cytoplasmic regions contain either an ITAM (Cyca-NILT1) or ITIMs (Cyca-NILT2). The tissue expression of these receptors is nearly identical, with the highest expression in the immunological organs. Peripheral blood leucocytes showed no detectable expression, but upon in vitro culture expressed NILT1, the activating receptor, and not the inhibitory NILT2 receptor. Southern blot analysis indicated that the NILT1 and NILT2 sequences belong to a multigene family. Analysis of the NILT Ig domain-encoding sequences amplified from both genomic DNA and cDNA revealed extensive haplotypic and allelic polymorphism. Database mining of the zebrafish genome identified several homologs on Chromosome 1, which also contains a cluster of class I major histocompatibility genes. This constellation is reminiscent of the TREM/NKp44 gene cluster and the HLA complex located on human Chromosome 6. The carp NILT genes form a unique cluster of innate immune receptors, which are highly polymorphic, and characterised by a new Ig structural subfamily and are distinct from the novel immune-type receptors (Nitrs) found in other fish species.

Amino Acid Motifs↗

The canine olfactory subgenome.

We identified 971 olfactory receptor (OR) genes in the dog genome, estimated to constitute approximately 80% of the canine OR repertoire. This was achieved by directed genomic DNA cloning of olfactory sequence tags as well as by mining the Celera canine genome sequences. The dog OR subgenome is estimated to have 12% pseudogenes, suggesting a functional repertoire similar to that of mouse and considerably larger than for humans. No novel OR families were discovered, but as many as 34 gene subfamilies were unique to the dog. "Fish-like" Class I ancient ORs constituted 18% of the repertoire, significantly more than in human and mouse. A set of 122 dog-human-mouse ortholog triplets was identified, with a relatively high fraction of Class I ORs. The elucidation of a large portion of the canine olfactory receptor gene superfamily, with some dog-specific attributes, may help us understand the unique chemosensory capacities of this species.

Animals↗

SNPing in the human genome.

More than a million genetic markers in the form of single nucleotide polymorphisms are now available for use in genotype-phenotype studies in humans. The application of new strategies for representational cloning and sequencing from genomes combined with the mining of high-quality sequence variations in clone overlaps of genomic and/or cDNA sequences has played an important role in generating this new resource. The focus of variation analysis is now shifting from the identification of new markers to their typing in populations, and novel typing strategies are rapidly emerging. Assay readouts on oligonucleotide arrays, in microtiter plates, gels, flow cytometers and mass spectrometers have all been developed, but decreasing cost and increasing throughput of DNA typing remain key if high-density genetic maps are to be applied on a large scale.

Chromosome Mapping↗

Computational inference and experimental validation of the nitrogen assimilation regulatory network in cyanobacterium Synechococcus sp. WH 8102.

Deciphering the regulatory networks encoded in the genome of an organism represents one of the most interesting and challenging tasks in the post-genome sequencing era. As an example of this problem, we have predicted a detailed model for the nitrogen assimilation network in cyanobacterium Synechococcus sp. WH 8102 (WH8102) using a computational protocol based on comparative genomics analysis and mining experimental data from related organisms that are relatively well studied. This computational model is in excellent agreement with the microarray gene expression data collected under ammonium-rich versus nitrate-rich growth conditions, suggesting that our computational protocol is capable of predicting biological pathways/networks with high accuracy. We then refined the computational model using the microarray data, and proposed a new model for the nitrogen assimilation network in WH8102. An intriguing discovery from this study is that nitrogen assimilation affects the expression of many genes involved in photosynthesis, suggesting a tight coordination between nitrogen assimilation and photosynthesis processes. Moreover, for some of these genes, this coordination is probably mediated by NtcA through the canonical NtcA promoters in their regulatory regions.

Bacterial Proteins↗

Multi-Omics and Integrative Analytics in Natural Products Discovery.

Natural products (NPs) have long been an essential source of new bioactive compounds for drug discovery; however, traditional methods for screening and isolating these compounds can be slow and often yield diminishing returns. Fortunately, advanced multi-omics and computational approaches present powerful solutions to these challenges. This review highlights innovative methodologies that integrate metabolomics, genomics, transcriptomics, and proteomics with bioinformatics and analytical chemistry to accelerate NP discovery. For instance, untargeted metabolomics platforms like high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Global Natural Products Social (GNPS) molecular networking allow for comprehensive profiling of new compounds, while targeted isotope-labeling strategies enhance this process. Additionally, genome and metagenome mining tools such as antibiotics and secondary metabolite analysis shell (antiSMASH), Deep Biosynthetic Gene Cluster (DeepBGC), and Pipeline for Reconstructing Integrated Syntheses of Metabolites (PRISM) quickly identify biosynthetic gene clusters (BGCs) in both cultured and uncultured organisms, often using heterologous expression to validate products. Transcriptomic analyses, including RNA sequencing (RNA-seq), co-expression networks, and fluxomics, help clarify how pathways are regulated, while quantitative proteomics techniques like tandem mass tags/isobaric tags for relative and absolute quantitation (TMT/iTRAQ) and label-free methods, along with chemoproteomics approaches such as cellular thermal shift assay and thermal proteome profiling (TPP), uncover molecular targets and their mechanisms of action. This review also places significant emphasis on the role of artificial intelligence (AI) and machine learning (ML) in integrating multi-omics data, spanning activities from constructing gene-metabolite correlation networks to leveraging knowledge graphs and graph neural networks for data fusion and functional prediction. Finally, this review concludes by discussing the synergistic benefits of multi-omics for natural-product discovery, addressing current technical challenges, and exploring future directions toward high-throughput, intelligent data integration for next-generation NP research.

Biological Products↗

Adplot: detection and visualization of repetitive patterns in complete genomes.

MOTIVATION: Repetitive DNA sequences are abundant in genomes and efficient mining of significant repeats is important as the first step of repetitive sequence research. Although many computational tools for the purpose, either automatic or visualization ones, have been developed, detection and analysis of approximate repeats are still non-trivial task. RESULTS: Auto Dot PLOT (Adplot), a dotplot-like repetitive pattern visualization program with a window filtering based on iid Bernoulli trials, is developed and applied to yeast chromosomes and human T cell receptor locus sequence. Typical examples found in yeast chromosomes 1 and 10 and a tandem repeat of periods longer than 10,000 bp in human T cell receptor locus are presented. A complex structure composed of both direct and palindromic repeats found in yeast chromosome 10 is also visualized as specific dot pattern. Computational time measured by a Pentium 3 PC for each yeast auto chromosome with a standard parameter setting is linearly scaled and below 10 s per one chromosome, indicating efficiency of the program. From the examples, it is shown that Adplot can visualize approximate local repeat structures and give us a diagnosis power for inferring a duplicational history of repeats. AVAILABILITY: Adplot can be obtained by an e-mail request.

Algorithms↗

Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish.

We mined the zebrafish genomic sequence database and identified contigs containing segments of several dopamine receptor genes. By using a polymerase chain reaction amplification strategy, we generated full-length cDNAs encoding a single dopamine D3 receptor and three distinct D2 receptor subtypes. Zebrafish dopamine receptor genes were mapped by using the T51 radiation hybrid panel. The D3 receptor gene (drd3) mapped to linkage group (LG) 24. The three D2 receptor genes were localized to LG 15 (drd2a), LG 16, (drd2b), and LG 5 (drd2c). With the exception of the drd2b gene, each of these map positions was syntenic with regions of human chromosomes containing orthologs of the zebrafish dopamine receptor genes. Whole-mount in situ hybridization was used to investigate expression of the D2 and D3 receptor genes. Expression of the drd3 gene was first detected at mid-somitogenesis and was particularly prominent in somites. Thereafter, the drd3 gene was expressed diffusely throughout the brain and spinal cord. The three D2 receptor genes were expressed throughout the central nervous system (CNS) in distinct but overlapping patterns. In early embryos, the drd2a gene was expressed exclusively in the epiphysis, whereas the drd2c gene was localized to the notochord. After 24 hpf, the drd2a, drd2b, and drd2c genes were differentially expressed throughout the CNS. The identification of dopamine receptor genes in zebrafish should allow us to use the power of zebrafish genetics to analyze the functional properties of this important class of neurotransmitter receptors.

Amino Acid Sequence↗

MHC class I-like genes in cattle, MHCLA, with similarity to genes encoding NK cell stimulatory ligands.

A comparative genomics approach for mining databases of expressed sequence tags (ESTs) was used to identify two members of a novel MHC class I gene family in cattle. These paralogous genes, named MHC class I-like gene family A1 ( MHCLA1) and MHCLA2, were shown by phylogenetic analysis to be related to human and mouse genes encoding NK cell stimulatory ligands, ULBP, RAET, H60 and Raet-1. Radiation hybrid mapping placed cattle MHCLA1 on BTA9, which, on the basis of existing comparative mapping data, identified the ULBP, RAET1, H60 and Raet1 genes as homologues of the cattle MHCLA genes. However, the human and mouse orthologues of MHCLA1 and MHCLA2 could not be defined due to extensive sequence divergence from all known members of the ULBP1/ RAET1/H60/Raet1 gene family. The cattle MHCLA1 molecule is predicted to be missing an alpha(3) domain, similar to the human and mouse homologues. Like the human ULBP genes, MHCLA1 was found to be transcribed constitutively in a variety of fetal and adult tissues by RT-PCR. The patterns of hybridization obtained by Southern blotting using MHCLA1 as a probe and DNA from 14 species representing five mammalian orders suggests that the MHCLA genes evolved rapidly in the Cetartiodactyla. Previous findings demonstrating that ULBPs serve as ligands for the NK cell NKG2D stimulatory receptor, and that this interaction can be blocked by a human cytomegalovirus glycoprotein that binds to ULBPs, suggests that the extensive divergence found among the cattle, human and mouse MHCLA homologues is due to selection exerted by viral pathogens.

Amino Acid Sequence↗

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis↗

Purification of an eight subunit RNA polymerase I complex in Trypanosoma brucei.

Trypanosoma brucei harbors a unique multifunctional RNA polymerase (pol) I which transcribes, in addition to ribosomal RNA genes, the gene units encoding the major cell surface antigens variant surface glycoprotein and procyclin. In consequence, this RNA pol I is recruited to three structurally different types of promoters and sequestered to two distinct nuclear locations, namely the nucleolus and the expression site body. This versatility may require parasite-specific protein-protein interactions, subunits or subunit domains. Thus far, data mining of trypanosomatid genomes have revealed 13 potential RNA pol I subunits which include two paralogous sets of RPB5, RPB6, and RPB10. Here, we analyzed a cDNA library prepared from procyclic insect form T. brucei and found that all 13 candidate subunits are co-expressed. Moreover, we PTP-tagged the largest subunit TbRPA1, tandem affinity-purified the enzyme complex to homogeneity, and determined its subunit composition. In addition to the already known subunits RPA1, RPA2, RPC40, 1RPB5, and RPA12, the complex contained RPC19, RPB8, and 1RPB10. Finally, to evaluate the absence of RPB6 in our purifications, we used a combination of epitope-tagging and reciprocal coimmunoprecipitation to demonstrate that 1RPB6 but not 2RPB6 binds to RNA pol I albeit in an unstable manner. Collectively, our data strongly suggest that T. brucei RNA pol I binds a distinct set of the RPB5, RPB6, and RPB10 paralogs.

Amino Acid Sequence↗

The genes encoding cAMP-dependent protein kinase catalytic subunit homologues of the microsporidia Encephalitozoon intestinalis and E. cuniculi: molecular characterisation and phylogenetic analysis.

A gene encoding a protein kinase was identified by homology-based PCR amplification in Encephalitozoon intestinalis, a microsporidian parasite pathogenic to humans, and its orthologue has been identified by database mining in the genome of the related species E. cuniculi, whose sequence has been recently published. Phylogenetic analysis revealed that the proteins encoded by these genes are homologues of the cAMP-dependent protein kinase catalytic subunits (PKAc). Southern blot analysis indicated that the EiPKAc gene is present in two copies in the E. intestinalis genome, whereas the E. cuniculi orthologue (EcPKAc) is a single copy gene. RT-PCR data showed that the EiPKAc gene is expressed in at least one of the intracellular stages during infection of the mammalian host cell by E. intestinalis.

Amino Acid Sequence↗

The latest phospholipase C, PLCeta, is implicated in neuronal function.

Members of the phosphoinositide-specific phospholipase C (PLC) family have key roles in cell signalling. In response to many extracellular stimuli, such as hormones, neurotransmitters, antigens and growth factors, PLCs catalyse the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], thereby generating two well-established second messengers, inositol (1,4,5)-trisphosphate and diacylglycerol. Eleven PLC isozymes encoded by different genes have been identified in mammals and, on the basis of their structure and sequence relationships, have been classified into five families designated PLCbeta (1-4), PLCgamma (1 and 2), PLCdelta (1, 3 and 4), PLCepsilon (1) and PLCzeta (1). All PLCs contain the catalytic X and Y domain, in addition to other regulatory domains including the C2 domain and the EF-hand domain. In 2005, four groups independently identified an entirely new family of PLCs--eta1 and eta2--using data mining of mammalian genomes. The properties of the PLCeta enzyme suggest that it might act as a Ca(2+) sensor, in particular, functioning during formation and maintenance of the neuronal network in the postnatal brain.

Animals↗

The histamine H4 receptor as a new therapeutic target for inflammation.

Following the sequencing of the human genome, data-mining efforts have revealed the existence of a new histamine receptor that is expressed at high levels in mast cells and leukocytes. The histamine H(4) receptor has a distinct pharmacological profile and the first compounds that act selectively on the H(4) receptor have been developed. Initial experiments in vivo with H(4) receptor antagonists indicate a role for the H(4) receptor in inflammatory conditions.

Amino Acid Sequence↗

Patenting human genes: when economic interests trump logic and ethics.

To date, over 5,000 applications have been filed with United States Patent Office for patents on human genes. More than 1,500 of these applications have been granted. Other jurisdictions are experiencing a similar rush to mine and protect genomic gold. This paper argues that although many jurisdictions allow the patenting of human genes, this is ethically indefensible and amounts to an unjustified appropriation of a general human heritage. Economic and legal arguments in favour of patenting are considered and rejected. Reference is made to the Wellcome Trust Consortium's initiative and the Merck Gene Index Project, which place patented genetic information into the public domain.

Biotechnology↗

Iron homeostasis: insights from genetics and animal models.

Disorders that perturb iron balance are among the most prevalent human diseases, but until recently iron transport remained poorly understood. Over the past five years, genetic studies of patients with inherited iron homeostasis disorders and the analysis of mutant mice, rats and zebrafish have helped to identify several important iron-transport proteins. With information being mined from the genomes of four species, the study of iron metabolism has benefited enormously from positional-cloning efforts. Complementing the genomic strategy, targeted mutagenesis in mice has produced new models of human iron diseases. The animal models described in this review offer valuable tools for investigating iron homeostasis in vivo.

Animals↗