Cell, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Genetics, Год журнала: 2023, Номер 224(1)
Опубликована: Март 3, 2023
Abstract The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins noncoding RNAs). GO annotations cover from organisms across tree life as well viruses, though most function knowledge currently derives experiments carried out in relatively small number model organisms. Here, we provide an updated overview knowledgebase, efforts broad, international consortium scientists that develops, maintains, updates knowledgebase. consists three components: (1) GO—a computational structure describing functional characteristics genes; (2) annotations—evidence-supported statements asserting specific product has particular characteristic; (3) Causal Activity Models (GO-CAMs)—mechanistic models molecular “pathways” (GO biological processes) created by linking multiple using defined relations. Each these components continually expanded, revised, response to newly published discoveries receives extensive QA checks, reviews, user feedback. For each components, description current contents, recent developments keep up date with new discoveries, guidance on how users can best make use data provide. We conclude future directions for project.
Язык: Английский
Процитировано
1285
Protein Science, Год журнала: 2021, Номер 31(1), С. 8 - 22
Опубликована: Окт. 30, 2021
Phylogenetics is a powerful tool for analyzing protein sequences, by inferring their evolutionary relationships to other proteins. However, phylogenetics analyses can be challenging: they are computationally expensive and must performed carefully in order avoid systematic errors artifacts. Protein Analysis THrough Evolutionary Relationships (PANTHER; http://pantherdb.org) publicly available, user-focused knowledgebase that stores the results of an extensive phylogenetic reconstruction pipeline includes computational manual processes quality control steps. First, fully reconciled trees (including ancestral sequences) reconstructed set "reference" sequences obtained from sequenced genomes organisms across tree life. Second, resulting manually reviewed annotated with function evolution events: inferred gains losses along branches tree. Here, we describe detail current contents PANTHER, how those generated, used variety applications. The PANTHER downloaded or accessed via API. In addition, provides software tools facilitate application common sequence analysis tasks: exploring genome gene function; performing "enrichment analysis" lists genes; annotating single large batch homology; assessing likelihood genetic variant at particular site will have deleterious effects.
Язык: Английский
Процитировано
1200
Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(8), С. 625 - 640
Опубликована: Июнь 21, 2023
Язык: Английский
Процитировано
148
Nucleic Acids Research, Год журнала: 2024, Номер 53(D1), С. D609 - D617
Опубликована: Ноя. 18, 2024
The aim of the UniProt Knowledgebase (UniProtKB; https://www.uniprot.org/) is to provide users with a comprehensive, high-quality and freely accessible set protein sequences annotated functional information. In this publication, we describe ongoing changes our production pipeline limit available in UniProtKB high-quality, non-redundant reference proteomes. We continue manually curate scientific literature add latest data use machine learning techniques. also encourage community curation ensure key publications are not missed. an update on automatic annotation methods used by predict information for unreviewed entries describing unstudied proteins. Finally, updates website described, including new tab linking genomic recognition its value community, database has been awarded Global Core Biodata Resource status.
Язык: Английский
Процитировано
142
Nature Methods, Год журнала: 2024, Номер 21(3), С. 465 - 476
Опубликована: Янв. 31, 2024
Abstract Intrinsically disordered regions (IDRs) are ubiquitous across all domains of life and play a range functional roles. While folded generally well described by stable three-dimensional structure, IDRs exist in collection interconverting states known as an ensemble. This structural heterogeneity means that largely absent from the Protein Data Bank, contributing to lack computational approaches predict ensemble conformational properties sequence. Here we combine rational sequence design, large-scale molecular simulations deep learning develop ALBATROSS, deep-learning model for predicting dimensions IDRs, including radius gyration, end-to-end distance, polymer-scaling exponent asphericity, directly sequences at proteome-wide scale. ALBATROSS is lightweight, easy use accessible both locally installable software package point-and-click-style interface via Google Colab notebooks. We first demonstrate applicability our predictors examining generalizability sequence–ensemble relationships IDRs. Then, leverage high-throughput nature characterize sequence-specific biophysical behavior within between proteomes.
Язык: Английский
Процитировано
100
Journal of Pharmaceutical Analysis, Год журнала: 2023, Номер 13(8), С. 836 - 850
Опубликована: Июль 1, 2023
Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth information, with its application to neuroscience termed neuroinformatics. Data mining enabled the generation new hypotheses based on differentially regulated biological molecules associated disease mechanisms, which can be tested experimentally for improved diagnostic therapeutic targeting neurodegenerative diseases. Importantly, integrating multi-omics data using systems bioinformatics approach will advance understanding layered interactive network regulation that exchanges systemic knowledge facilitate development comprehensive human brain profile. In this review, we first summarize studies utilizing from individual type analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, spatial omics, pertaining Alzheimer's disease, Parkinson's multiple sclerosis. We then discuss integration approaches, independent unsupervised methods, more intuitive informative interpretation obtained across different layers. further assess integrate provide convoluted insights offer proof-of-concept proposition towards reconstruction networks. Finally, recommend combination high dimensional experimental validation achieve translational applications biomarker discovery, development, elucidation mechanisms. conclude future perspectives opportunities applying integrative precision phenotyping diseases personalized medicine.
Язык: Английский
Процитировано
48
Cell, Год журнала: 2023, Номер 186(17), С. 3642 - 3658.e32
Опубликована: Июль 11, 2023
A system for programmable export of RNA molecules from living cells would enable both non-destructive monitoring cell dynamics and engineering capable delivering executable programs to other cells. We developed genetically encoded cellular exporters, inspired by viruses, that efficiently package secrete cargo mammalian within protective nanoparticles. Exporting sequencing barcodes enabled population with clonal resolution. Further, incorporating fusogens into the nanoparticles, we demonstrated delivery, expression, functional activity exported mRNA in recipient term these systems COURIER (controlled output uptake interrogation, regulation). enables measurement establishes a foundation hybrid gene therapies based on cell-to-cell delivery RNA.
Язык: Английский
Процитировано
45
Pharmacological Research, Год журнала: 2023, Номер 198, С. 106999 - 106999
Опубликована: Ноя. 19, 2023
Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules a diet rich vegetables fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) biogenetically morphologically comparable to mammalian transport molecules, including miRNAs. However, the biological functions of PDEVs not fully understood, standard isolation protocols lacking. Here, were isolated from four foods combination ultracentrifugation size exclusion chromatography, evaluated as vehicles for enhanced synthetic In addition, role food-derived carriers dietary (poly)phenols other secondary metabolites was investigated. broccoli, pomegranate, apple, orange efficiently characterized. all sources, 4 miRNA families present tissues EVs. miRNAs broccoli fruit-derived showed reduced RNase degradation ferried inside exposed cells. transfected ath-miR159a, ath-miR162a-3p, ath-miR166b-3p, ath-miR396b-5p toxic effects on human cells, did natural alone. trace amounts phytochemicals, flavonoids, anthocyanidins, phenolic acids, or glucosinolates. Thus, can act nanocarriers functional that could be used RNA-based therapy.
Язык: Английский
Процитировано
43
Computational and Structural Biotechnology Journal, Год журнала: 2024, Номер 23, С. 1154 - 1168
Опубликована: Март 1, 2024
In recent years, the role of bioinformatics and computational biology together with omics techniques transcriptomics has gained tremendous importance in biomedicine healthcare, particularly for identification biomarkers precision medicine drug discovery. Differential gene expression (DGE) analysis is one most used RNA-sequencing (RNA-seq) data analysis. This tool, which typically various RNA-seq processing applications, allows differentially expressed genes across two or more sample sets. Functional enrichment analyses can then be performed to annotate contextualize resulting lists. These studies provide valuable information about disease-causing biological processes help identifying molecular targets novel therapies. review focuses on differential pipelines commonly identify specific discuss advantages disadvantages these techniques.
Язык: Английский
Процитировано
32
Science, Год журнала: 2024, Номер 384(6692)
Опубликована: Апрель 4, 2024
Males and females exhibit profound differences in immune responses disease susceptibility. However, the factors responsible for sex tissue immunity remain poorly understood. Here, we uncovered a dominant role type 2 innate lymphoid cells (ILC2s) shaping sexual dimorphism within skin. Mechanistically, negative regulation of ILC2s by androgens leads to reduction dendritic cell accumulation activation males, along with reduced immunity. Collectively, our results reveal androgen-ILC2-dendritic axis controlling dimorphism. Moreover, this work proposes that set points are defined dual action hormones microbiota, strength local microbiota calibrating its tone.
Язык: Английский
Процитировано
30