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At least 145 records · Page 8Linked to original sources

PubMed2026

A conserved distal-tail helical extension defines a tailspike attachment architecture in Gram-negative siphophages.

Rapid growth of bacteriophage genome collections has outpaced functional annotation of tail-tip proteins, limiting comparative analysis of host-recognition structures. Starting from a shared distal-tail gene organization in the Salmonella phages 9NA and Jersey, I developed a morphogenetic bioinformatic framework integrating gene synteny, sequence comparison, profile hidden Markov model (HMM) screening, structural evidence, structure-aware searching, and AlphaFold modeling. Comparison with the experimentally characterized lambda and Sf11 tail assemblies identified a predominantly alpha-helical C-terminal extension of the distal-tail (DT) protein associated with tailspike attachment, termed the distal-tail helical extension (DT-helix). Screening 541,986 proteins from 5167 complete NCBI RefSeq tailed-phage genomes, followed by evidence-based evaluation of sequence, genomic context, and structural architecture, identified 165 curated DT-helical-extension-associated phages. Their DT proteins segregated into six sequence groups. In the four principal multi-member groups, cognate tailspikes showed group-specific conservation in proximal N-terminal regions but substantially greater downstream diversity, consistent with sequence constraint at the DT-tailspike attachment boundary. A complementary ProstT5/Foldseek search supported the established groups but revealed no convincing additional highly divergent family. Together with the experimentally characterized Sf11 attachment interface, these findings define a recurrent morphogenetic architecture linking conserved distal-tail scaffolds to more variable receptor-binding proteins across siphophages infecting Gram-negative bacteria. Although universal exchangeability is not established, the identified scaffold-receptor-binding boundaries provide a framework for molecular characterization and rational phage engineering. Accession-level information for the 165 curated phages is available through PhageTailDB.

Viral Tail Proteins↗

PubMed2002

HMM-based databases in InterPro.

Protein family databases are an important resource for protein annotation and understanding protein evolution and function. In recent years hidden Markov models (HMMs) have become one of the key technologies used for detection of members of these families. This paper reviews the Pfam, TIGRFAMs and SMART databases that use the profile-HMMs provided by the HMMER package.

Computational Biology↗

PubMed2026

Draft genome assembly of the green-bronze dung beetle, Onthophagus orpheus.

Dung beetles (Coleoptera: Scarabaeinae) are ecologically important insects, yet genomic resources for this diverse lineage remain limited. Here, we present a high-quality genome assembly for Onthophagus orpheus, an understudied species that is abundant in urban forests in the eastern United States. The assembled genome is a scaffold-level assembly, with a high degree of genic completeness as assessed by Benchmarking Universal Single-Copy Ortholog (BUSCO) analyses, indicating robust representation of conserved protein-coding genes. Structural and functional annotation recovered a comprehensive gene set consistent with expectations for coleopteran genomes. This genome assembly provides an important resource for future work on the behavioral ecology and population genetics of Onthophagus orpheus, specifically, and Scarabaeidae more broadly.

Onthophagus↗

PubMed2003

Accelerating comparative genomics using parallel computing.

In the past decade there has been an increase in the number of completely sequenced genomes due to the race of multibillion-dollar genome-sequencing projects. The enormous biological sequence data thus flooding into the sequence databases necessitates the development of efficient tools for comparative genome sequence analysis. The information deduced by such analysis has various applications viz. structural and functional annotation of novel genes and proteins, finding gene order in the genome, gene fusion studies, constructing metabolic pathways etc. Such study also proves invaluable for pharmaceutical industries, such as in silico drug target identification and new drug discovery. There are various sequence analysis tools available for mining such useful information of which FASTA and Smith-Waterman algorithms are widely used. However, analyzing large datasets of genome sequences using the above codes seems to be impractical on uniprocessor machines. Hence there is a need for improving the performance of the above popular sequence analysis tools on parallel cluster computers. Performance of the Smith-Waterman (SSEARCH) and FASTA programs were studied on PARAM 10000, a parallel cluster of workstations designed and developed in-house. FASTA and SSEARCH programs, which are available from the University of Virginia, were ported on PARAM and were optimized. In this era of high performance computing, where the paradigm is shifting from conventional supercomputers to the cost-effective general-purpose cluster of workstations and PCs, this study finds extreme relevance. Good performance of sequence analysis tools on a cluster of workstations was demonstrated, which is important for accelerating identification of novel genes and drug targets by screening large databases.

Algorithms↗

PubMed2001

iProClass: an integrated, comprehensive and annotated protein classification database.

The iProClass database is an integrated resource that provides comprehensive family relationships and structural and functional features of proteins, with rich links to various databases. It is extended from ProClass, a protein family database that integrates PIR superfamilies and PROSITE motifs. The iProClass currently consists of more than 200,000 non-redundant PIR and SWISS-PROT proteins organized with more than 28,000 superfamilies, 2600 domains, 1300 motifs, 280 post-translational modification sites and links to more than 30 databases of protein families, structures, functions, genes, genomes, literature and taxonomy. Protein and family summary reports provide rich annotations, including membership information with length, taxonomy and keyword statistics, full family relationships, comprehensive enzyme and PDB cross-references and graphical feature display. The database facilitates classification-driven annotation for protein sequence databases and complete genomes, and supports structural and functional genomic research. The iProClass is implemented in Oracle 8i object-relational system and available for sequence search and report retrieval at http://pir.georgetown.edu/iproclass/.

Databases, Factual↗

PubMed2002

Bioinformatics of large-scale protein interaction networks.

We survey recent techniques for construction and prediction of large-scale protein interaction networks, focusing on computational processing steps. Special emphasis is placed on critical assessment of data completeness and reliability of the various approaches. Once built, protein interaction networks can be used for functional annotation or to generate higher-level biological hypotheses on pathways.

Bacterial Proteins↗

PubMed2000

Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.

We have carried out a human cDNA sequencing project to accumulate information regarding the coding sequences of unidentified human genes. As an extension of the preceding reports, we herein present the entire sequences of 150 cDNA clones of unknown human genes, named KIAA1294 to KIAA1443, from two sets of size-fractionated human adult and fetal brain cDNA libraries. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here reached 4.8 kb and 2.7 kb (910 amino acid residues), respectively. From sequence similarities and protein motifs, 73 predicted gene products were functionally annotated and 97% of them were classified into the following four functional categories: cell signaling/communication, nucleic acid management, cell structure/motility and protein management. Additionally, the chromosomal loci of the genes were assigned by using human-rodent hybrid panels for those genes whose mapping data were not available in the public databases. The expression profiles of the genes were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.

Adult↗

PubMed1999

The SWISS-PROT protein sequence data bank and its supplement TrEMBL in 1999.

SWISS-PROT is a curated protein sequence database which strives to provide a high level of annotation (such as the description of the function of a protein, its domain structure, post-translational modifications, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recent developments of the database include: cross-references to additional databases; a variety of new documentation files and improvements to TrEMBL, a computer annotated supplement to SWISS-PROT. TrEMBL consists of entries in SWISS-PROT-like format derived from the translation of all coding sequences (CDS) in the EMBL nucleotide sequence database, except the CDS already included in SWISS-PROT. The URLs for SWISS-PROT on the WWW are: http://www.expasy.ch/sprot and http://www. ebi.ac.uk/sprot

Amino Acid Sequence↗

PubMed2000

The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000.

SWISS-PROT is a curated protein sequence database which strives to provide a high level of annotation (such as the description of the function of a protein, its domains structure, post-translational modifications, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recent developments of the database include format and content enhancements, cross-references to additional databases, new documentation files and improvements to TrEMBL, a computer-annotated supplement to SWISS-PROT. TrEMBL consists of entries in SWISS-PROT-like format derived from the translation of all coding sequences (CDSs) in the EMBL Nucleotide Sequence Database, except the CDSs already included in SWISS-PROT. We also describe the Human Proteomics Initiative (HPI), a major project to annotate all known human sequences according to the quality standards of SWISS-PROT. SWISS-PROT is available at: http://www.expasy.ch/sprot/ and http://www.ebi.ac.uk/swissprot/

Animals↗

PubMed2026

A Network Pharmacology and Molecular Docking Study of TongBi Formula for Osteoarthritis.

This study applied network pharmacology combined with molecular docking to predict the potential therapeutic targets and molecular mechanisms of TongBi Formula (TBF) in osteoarthritis (OA). Active components and corresponding targets of TBF were retrieved from the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform, while OA-related targets were collected from Online Mendelian Inheritance in Man, GeneCards, DrugBank, and Therapeutic Target Database. A network visualization and analysis software was used to construct compound-target and protein-protein interaction (PPI) networks. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery platform. Molecular docking analysis was conducted using a molecular docking software to evaluate the predicted binding affinity between key active compounds and core target proteins. A total of 47 overlapping targets between TBF and OA were identified. PPI network analysis highlighted JUN, RELA, IL6, MAPK1, and IL10 as potential hub targets. Enrichment analysis suggested that TBF may regulate inflammation, lipid metabolism, and multiple intracellular signaling pathways associated with OA progression. Molecular docking results demonstrated favorable predicted binding affinities between core active compounds and key OA-related protein targets. These findings provide a computational framework for understanding the potential mechanisms of TBF against OA and support further experimental validation.

Molecular Docking Simulation↗

PubMed2000

From fold to function predictions: an apoptosis regulator protein BID.

With the rapidly increasing pace of genome sequencing projects and the resulting flood of predicted amino acid sequences of uncharacterized proteins, protein sequence analysis, and in particular, protein structure prediction is quickly gaining in importance. Prediction algorithms can be used for preliminary annotation of newly sequenced proteins and, at least in some cases, provide insights into their function and specific mode of action. Such annotations for several microbial genomes were performed by several groups and placed in public domain for evaluation. An example presented in this work comes from a related project of structural and functional predictions for proteins involved in the process of controlled cell death (apoptosis). The BID protein belongs to an important class of regulators of apoptosis identified by short sequence motifs. Here, several fold prediction methods are used to build a series of three-dimensional models. Structure analysis of the models with reference to the biological data available allows selection of the most appropriate model. It is found that the most likely structural model of BID is built on the structure of Bcl-X(L). The model is discussed in terms of experimental data on specific proteolytic cleavage of BID and its effect on BID interactions with other proteins and membranes.

Algorithms↗

PubMed2003

ELISA: structure-function inferences based on statistically significant and evolutionarily inspired observations.

UNLABELLED: The problem of functional annotation based on homology modeling is primary to current bioinformatics research. Researchers have noted regularities in sequence, structure and even chromosome organization that allow valid functional cross-annotation. However, these methods provide a lot of false negatives due to limited specificity inherent in the system. We want to create an evolutionarily inspired organization of data that would approach the issue of structure-function correlation from a new, probabilistic perspective. Such organization has possible applications in phylogeny, modeling of functional evolution and structural determination. ELISA (Evolutionary Lineage Inferred from Structural Analysis, http://romi.bu.edu/elisa) is an online database that combines functional annotation with structure and sequence homology modeling to place proteins into sequence-structure-function "neighborhoods". The atomic unit of the database is a set of sequences and structural templates that those sequences encode. A graph that is built from the structural comparison of these templates is called PDUG (protein domain universe graph). We introduce a method of functional inference through a probabilistic calculation done on an arbitrary set of PDUG nodes. Further, all PDUG structures are mapped onto all fully sequenced proteomes allowing an easy interface for evolutionary analysis and research into comparative proteomics. ELISA is the first database with applicability to evolutionary structural genomics explicitly in mind. AVAILABILITY: The database is available at http://romi.bu.edu/elisa.

Amino Acid Sequence↗

PubMed1998

The SWISS-PROT protein sequence data bank and its supplement TrEMBL in 1998.

SWISS-PROT (http://www.expasy.ch/) is a curated protein sequence database which strives to provide a high level of annotations (such as the description of the function of a protein, its domains structure, post-translational modifications, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recent developments of the database include: an increase in the number and scope of model organisms; cross-references to two additional databases; a variety of new documentation files and improvements to TrEMBL, a computer annotated supplement to SWISS-PROT. TrEMBL consists of entries in SWISS-PROT-like format derived from the translation of all coding sequences (CDS) in the EMBL nucleotide sequence database, except the CDS already included in SWISS-PROT.

Amino Acid Sequence↗

PubMed2002

Visualizing the genome: techniques for presenting human genome data and annotations.

BACKGROUND: In order to take full advantage of the newly available public human genome sequence data and associated annotations, biologists require visualization tools ("genome browsers") that can accommodate the high frequency of alternative splicing in human genes and other complexities. RESULTS: In this article, we describe visualization techniques for presenting human genomic sequence data and annotations in an interactive, graphical format. These techniques include: one-dimensional, semantic zooming to show sequence data alongside gene structures; color-coding exons to indicate frame of translation; adjustable, moveable tiers to permit easier inspection of a genomic scene; and display of protein annotations alongside gene structures to show how alternative splicing impacts protein structure and function. These techniques are illustrated using examples from two genome browser applications: the Neomorphic GeneViewer annotation tool and ProtAnnot, a prototype viewer which shows protein annotations in the context of genomic sequence. CONCLUSION: By presenting techniques for visualizing genomic data, we hope to provide interested software developers with a guide to what features are most likely to meet the needs of biologists as they seek to make sense of the rapidly expanding body of public genomic data and annotations.

Alternative Splicing↗

PubMed2026

ECLIPSE: exploring the dark proteome of ESKAPE pathogens through the sequence similarity network of the Protein Universe Atlas.

MOTIVATION: The accelerating crisis of antimicrobial resistance among the critical so-called ESKAPE pathogens demands the urgent identification of novel molecular targets. However, a substantial fraction of ESKAPE proteomes remains functionally uncharacterized, with many genes annotated as encoding hypothetical proteins. These protein sequences often lack significant similarity to known protein families when conventional homology-based annotation methods are used and thus remain "dark". This limits our ability to explore their roles in pathogenicity, and it is thus crucial to bridge this substantial gap in pathogen biology by developing new strategies to illuminate these "dark" regions of the ESKAPE pan-proteome. RESULTS: We introduce ECLIPSE (ESKAPE Connectome Linkage and Inference for Proteome Sequence Exploration), a network-based computational framework that systematically identifies and prioritizes functionally dark protein families in ESKAPE pan-proteomes. ECLIPSE embeds target ESKAPE pathogen proteomes within the global sequence similarity network of the Protein Universe Atlas. It detects connected components composed entirely of unannotated proteins, called the "dark proteome." As a case study, we applied ECLIPSE to a pan-proteome of 3 460 657 protein sequences from 635 strains of Pseudomonas aeruginosa (PA). ECLIPSE identified 120 985 proteins (4%) residing in completely dark connected components. Furthermore, we have performed a taxonomic diversity analysis using normalized Shannon indices to characterize each dark component by its enrichment in ESKAPE pathogens. The analysis utilized the evenness (E) value (see Methods 2.1), which distinguishes Pseudomonas-specific (target-specific) from ESKAPE-enriched dark components. We then developed the Dark Proteome Prioritization Score (DPPS), a composite multidimensional scoring framework (see Methods 2.5). It ranks these dark components by biological relevance across four orthogonal axes: (i) functional darkness, (ii) P. aeruginosa proportion in the Atlas, (iii) AMR-clade taxonomic restriction, and (iv) conservation across the 635 P. aeruginosa strains. This framework outputs a robust four-tier scoring system; the prioritized Tier I components were validated by weight sensitivity analysis and remained stable across 500 Monte Carlo weight perturbations. Structural characterization of one of the top-ranked ESKAPE-enriched dark components revealed that it belongs to the beta-barrel fold DUF1302 (PF06980) family, for which no experimentally solved three-dimensional structure exists in the PDB. The genomic context analysis indicates that it is co-localized with a LuxR-type transcriptional regulator. Collectively, ECLIPSE identifies evolutionarily conserved, structurally defined, and functionally dark proteins enriched across ESKAPE pathogens; these dark proteins can further be utilized as alternative antimicrobial targets for experimental characterization. AVAILABILITY AND IMPLEMENTATION: The source code and dataset are available for free at: Github: https://github.com/surabhilata/ECLIPSE.git, Zenodo: DOI: 10.5281/zenodo.21064323.

Proteome↗

PubMed2013

Structural insights into adeno-associated virus serotype 5.

The adeno-associated viruses (AAVs) display differential cell binding, transduction, and antigenic characteristics specified by their capsid viral protein (VP) composition. Toward structure-function annotation, the crystal structure of AAV5, one of the most sequence diverse AAV serotypes, was determined to 3.45-Å resolution. The AAV5 VP and capsid conserve topological features previously described for other AAVs but uniquely differ in the surface-exposed HI loop between βH and βI of the core β-barrel motif and have pronounced conformational differences in two of the AAV surface variable regions (VRs), VR-IV and VR-VII. The HI loop is structurally conserved in other AAVs despite amino acid differences but is smaller in AAV5 due to an amino acid deletion. This HI loop is adjacent to VR-VII, which is largest in AAV5. The VR-IV, which forms the larger outermost finger-like loop contributing to the protrusions surrounding the icosahedral 3-fold axes of the AAVs, is shorter in AAV5, creating a smoother capsid surface topology. The HI loop plays a role in AAV capsid assembly and genome packaging, and VR-IV and VR-VII are associated with transduction and antigenic differences, respectively, between the AAVs. A comparison of interior capsid surface charge and volume of AAV5 to AAV2 and AAV4 showed a higher propensity of acidic residues but similar volumes, consistent with comparable DNA packaging capacities. This structure provided a three-dimensional (3D) template for functional annotation of the AAV5 capsid with respect to regions that confer assembly efficiency, dictate cellular transduction phenotypes, and control antigenicity.

Capsid Proteins↗

PubMed2026

Chromosome-level genome assembly of Manglietia pachyphylla.

Manglietia pachyphylla, an endangered evergreen tree within the Magnoliaceae family, is renowned for its exceptional ornamental value in landscape horticulture. Despite its classification as a Category II nationally protected plant species in China, the genetic basis of its adaptive traits and conservation priorities remains poorly understood. To address this, we present the first chromosome-scale genome assembly of M. pachyphylla utilizing an integrated approach combining PacBio HiFi long-read and Hi-C chromosome conformation capture sequencing technologies. The assembled genome spans 2.15 Gb (contig N50 = 43.57 Mb), exhibiting a heterozygosity rate of 0.78% and repeat content of 78.64%, predominantly comprising long terminal repeat (LTR) retrotransposons (52.86%). Hi-C scaffolding anchored 99.57% of the assembly to 19 pseudochromosomes, achieving a BUSCO completeness score of 96.4%. Annotation revealed 42,505 putative protein-coding genes, with 84.46% of predicted genes were functionally annotated. Phylogenomic analysis positioned M. pachyphylla and Oyama sieboldii clustered together in a well-supported group. This high-contiguity genome assembly enables future investigations into adaptive evolution, functional genomics, and evidence-based conservation strategies for this endangered species.

Chromosomes, Plant↗

PubMed2002

Enzyme function less conserved than anticipated.

The level of sequence similarity that implies similarity in protein structure is well established. Recently, many groups proposed thresholds for similarity in sequence implying similarity in enzymatic function. All previous results suggest the strong conservation of enzymatic function above levels of 50% pairwise sequence identity. Here, I argue that all groups substantially overestimated the conservation of enzyme function because their data sets were either too biased, or too small. An unbiased analysis suggested that less than 30% of the pair fragments above 50% sequence identity have entirely identical EC numbers. Another surprising finding was that even BLAST E-values below 10(-50) did not suffice to automatically transfer enzyme function without errors. As expected, most misclassifications originated from similarities in relatively short regions and/or from transferring annotations for different domains. Both problems cannot be corrected easily by adjusting the thresholds for automatic transfer of genome annotations. A score relating sequence identity to alignment length (distance from HSSP-threshold) outperformed statistical BLAST scores for high sequence similarity. In particular, the distance score allowed error-free transfer of enzyme function for the 10% most similar enzyme pairs. The results illustrated how difficult it is to assess the conservation of protein function and to guarantee error-free genome annotations, in general: sets with millions of pair comparisons might not suffice to arrive at statistically significant conclusions. In practice, the revised detailed estimates for the sequence conservation of enzyme function may provide important benchmarks for everyday sequence analysis and for more cautious automatic genome annotations.

Amino Acid Sequence↗