PubMed Health⌕ Search

PubMed · 15454675

Bioinformatic approaches to assigning protein function from novel sequence data.

Abstract

The current pace of functional genomic initiatives and genome sequencing projects has provided researchers with a bewildering array of sequence and biological data to analyze. The disease system-driven approach to identifying key genes frequently identifies nucleotide and protein sequences for which the gene and protein function are not known in sufficient detail to allow informed follow-up. Using a range of bioinformatic tools and sequence-based clues, most of unassigned sequences can now be annotated. This chapter takes as an example an unannotated expressed sequence tag, describing how to identify its related gene, and how to annotate the encoded protein using sequence, profile, and structure-based annotation methodologies.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

David Michalovich, Richard Fagan. 2005. Bioinformatic approaches to assigning protein function from novel sequence data.. https://doi.org/10.1385/1-59259-836-6%3A313

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Phage bioinformatics tools: a review of computational approaches for bacteriophage research.

Rising clinical interest in phage therapy and the exponential growth of metagenomic sequence catalogues have driven a rapid expansion of bacteriophage bioinformatics. More than 80 dedicated tools, mostly published since 2020, now span identification, assembly, annotation, taxonomy, lifestyle prediction, defence-system detection, and host prediction. Aimed at experienced practitioners and developers, this review synthesizes the field through the lens of three successive computational paradigms: sequence homology, bounded by database completeness; machine learning, constrained by labelled training data; and foundation models, which now achieve Matthews correlation coefficients above 0.95 in identification tasks and, through structure-informed prediction, raise functional annotation to over half of phage genes. Furthermore, we map the upstream components, namely, gene callers, homology engines, protein language models, and structural search tools, that underpin most downstream pipelines, exposing shared infrastructure and ecosystem-level fragility when dependencies change. To translate this into practice, we propose web-based and command-line reference workflows calibrated to user expertise and sample types. Finally, we set an agenda for the next wave of tool development. Roughly half of phage genes still resist functional annotation despite structural methods; no broadly generalizable strain-level host predictor exists for phage therapy; varying true-positive rates (0%-97%) underscore the absence of standardized community benchmarks analogous to Critical Assessment of Structure Prediction or Critical Assessment of Metagenome Interpretation. As generative genome models begin designing synthetic phages, progress will depend less on producing standalone tools than on rigorous evaluation, interoperable infrastructure, and clinically meaningful prediction targets.

Computational Biology↗

Collective posterior inference from highly variable empirical replicates.

High-throughput experimental platforms now routinely generate data from dozens or hundreds of independent observations. Simulation-based inference (SBI) offers a powerful framework for estimating model parameters from such complex datasets, but standard methods struggle to scale to the noisy multiple-replicates regime without incurring prohibitive computational costs or careful hyperparameter tuning. Here, we introduce a new method for fast and robust collective posterior inference from multiple independent replicates using a robust product-of-experts aggregation scheme that automatically mitigates the influence of outliers. Evaluating it on synthetic and empirical evolutionary datasets, we find it achieves state-of-the-art estimation accuracy and computational efficiency, including inference from noisy observations. Our method is compatible with any SBI framework, providing a scalable, plug-and-play solution for inference from noisy multiple-replicate datasets.

Computational Biology↗

ReGAIN: a bioinformatics platform for assessing probabilistic co-occurrence between resistance genes in bacterial pathogens.

MOTIVATION: Multidrug-resistant bacterial pathogens continue to rise globally, yet scalable methods are needed to infer how resistance determinants co-occur across pathogen populations and to quantify conditional dependencies underlying co-occurrence and shared genetic context. RESULTS: We present ReGAIN (Resistance Gene Association and Inference Network), an open-source platform that applies Bayesian network structure learning to infer probabilistic, conditional dependency relationships among antibiotic resistance, heavy metal tolerance, stress response, and virulence determinants in bacteria. In contrast to pairwise co-occurrence analyses, ReGAIN reports conditional probabilities, relative risks, and absolute risk differences with confidence intervals to prioritize candidate relationships for downstream prioritization. Applied across ESKAPEE pathogens, ReGAIN recapitulated established resistance gene relationships and identified additional candidate patterns consistent with co-selection and shared genetic context. Together, these results support scalable, reproducible population-wide analysis of resistance networks for surveillance, comparative genomics and epidemiology. AVAILABILITY: ReGAIN analyses are performed using Python v3.11.5 and R v4.4.1 and is available as open-source software through Bioconda at {https://anaconda.org/bioconda/regain-cli}. Source code and documentation can be found at {https://github.com/ERBringHorvath/regain_CLI}. All genomes used in this publication were downloaded from the National Center for Biotechnology Information database. Large supplementary tables and results data from the ESKAPEE pathogen example network analyses can be downloaded from https://figshare.com/articles/dataset/ReGAIN_command_line_software_and_supplemental_figures_/28959431.

Computational Biology↗