In vivo CRISPR screening directly targeting testicular cells DOI Creative Commons
Yuki Noguchi, Yasuhito Onodera, Tatsuo Miyamoto

и другие.

Cell Genomics, Год журнала: 2024, Номер 4(3), С. 100510 - 100510

Опубликована: Март 1, 2024

CRISPR-Cas9 short guide RNA (sgRNA) library screening is a powerful approach to understand the molecular mechanisms of biological phenomena. However, its in vivo application currently limited. Here, we developed our previously established vitro revival method into an one identify factors involved spermatogenesis integrity by utilizing sperm capacitation as indicator. By introducing sgRNA testicular cells, successfully pinpointed retinal degeneration 3 (Rd3) gene significant factor spermatogenesis. Single-cell sequencing (scRNA-seq) analysis highlighted high expression Rd3 round spermatids, and proteomics indicated that interacts with mitochondria. To search for cell-type-specific signaling pathways based on scRNA-seq analyses, computational tool, Hub-Explorer. Through this, discovered modulates oxidative stress regulating mitochondrial distribution upon ciliogenesis induction. Collectively, system provides valuable decipher processes.

Язык: Английский

Expasy, the Swiss Bioinformatics Resource Portal, as designed by its users DOI Creative Commons
Séverine Duvaud, Chiara Gabella, Frédérique Lisacek

и другие.

Nucleic Acids Research, Год журнала: 2021, Номер 49(W1), С. W216 - W227

Опубликована: Апрель 1, 2021

Abstract The SIB Swiss Institute of Bioinformatics (https://www.sib.swiss) creates, maintains and disseminates a portfolio reliable state-of-the-art bioinformatics services resources for the storage, analysis interpretation biological data. Through Expasy (https://www.expasy.org), Resource Portal, scientific community worldwide, freely accesses more than 160 supporting wide range life science biomedical research areas. In 2020, was redesigned through user-centric approach, known as User-Centred Design (UCD), whose aim is to create user interfaces that are easy-to-use, efficient targeting intended community. This widely used in other fields such marketing, e-commerce, design mobile applications, still scarcely explored bioinformatics. total, around 50 people were actively involved, including internal stakeholders end-users. addition an optimised interface meets users' needs expectations, new version provides up-to-date accurate description high-quality based on standardised ontology, allowing connect functionally-related resources.

Язык: Английский

Процитировано

609
Building a knowledge graph to enable precision medicine DOI Creative Commons
Payal Chandak, Kexin Huang, Marinka Žitnik

и другие.

Scientific Data, Год журнала: 2023, Номер 10(1)

Опубликована: Фев. 2, 2023

Abstract Developing personalized diagnostic strategies and targeted treatments requires a deep understanding of disease biology the ability to dissect relationship between molecular genetic factors their phenotypic consequences. However, such knowledge is fragmented across publications, non-standardized repositories, evolving ontologies describing various scales biological organization genotypes clinical phenotypes. Here, we present PrimeKG, multimodal graph for precision medicine analyses. PrimeKG integrates 20 high-quality resources describe 17,080 diseases with 4,050,249 relationships representing ten major scales, including disease-associated protein perturbations, processes pathways, anatomical entire range approved drugs therapeutic action, considerably expanding previous efforts in disease-rooted graphs. contains an abundance ‘indications’, ‘contradictions’, ‘off-label use’ drug-disease edges that lack other graphs can support AI analyses how affect networks. We supplement PrimeKG’s structure language descriptions guidelines enable provide instructions continual updates as new data become available.

Язык: Английский

Процитировано

185
AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations DOI Creative Commons

Wen‐Kang Shen,

Si‐Yi Chen,

Zi-Quan Gan

и другие.

Nucleic Acids Research, Год журнала: 2022, Номер 51(D1), С. D39 - D45

Опубликована: Окт. 5, 2022

Abstract Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up new data provide a more comprehensive resource for TF research, we updated the Animal Factor Database (AnimalTFDB) version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) up-to-date functions. We refined family rules prediction pipeline predict TFs genome-wide protein from Ensembl. As result, predicted 274 633 genes 150 726 transcription cofactor AnimalTFDB 183 animal genomes, which 86 species than 3.0. Besides double volume, also added following annotations functions database: (i) variations (including mutations) on various human cancers other diseases; (ii) post-translational modification sites phosphorylation, acetylation, methylation ubiquitination sites) 8 species; (iii) regulation autophagy; (iv) annotation 38 (v) exact batch search allow users flexibly. is useful studying regulation, contains classification cofactors.

Язык: Английский

Процитировано

147
Evolutionary constraint and innovation across hundreds of placental mammals DOI
Matthew J. Christmas, Irene M. Kaplow, Diane P. Genereux

и другие.

Science, Год журнала: 2023, Номер 380(6643)

Опубликована: Апрель 27, 2023

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half have no functional annotations Encyclopedia of DNA Elements (ENCODE) resource. Changes genes regulatory associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast imperiled biodiversity offers distinctive power identifying genetic variants function organismal phenotypes.

Язык: Английский

Процитировано

137
The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information DOI Creative Commons
John H. Morris, Karthik Soman, Rabia E Akbas

и другие.

Bioinformatics, Год журнала: 2023, Номер 39(2)

Опубликована: Фев. 1, 2023

Abstract Motivation Knowledge graphs (KGs) are being adopted in industry, commerce and academia. Biomedical KG presents a challenge due to the complexity, size heterogeneity of underlying information. Results In this work, we present Scalable Precision Medicine Open Engine (SPOKE), biomedical connecting millions concepts via semantically meaningful relationships. SPOKE contains 27 million nodes 21 different types 53 edges 55 downloaded from 41 databases. The graph is built on framework 11 ontologies that maintain its structure, enable mappings facilitate navigation. weekly by python scripts which download each resource, check for integrity completeness, then create ‘parent table’ edges. Graph queries translated REST API users can submit searches directly an or graphical user interface. Conclusions/Significance: enables integration seemingly disparate information support precision medicine efforts. Availability implementation neighborhood explorer available at https://spoke.rbvi.ucsf.edu. Supplementary data Bioinformatics online.

Язык: Английский

Процитировано

44
PubChem 2025 update DOI Creative Commons
Sunghwan Kim, Jie Chen, Tiejun Cheng

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 53(D1), С. D1516 - D1525

Опубликована: Ноя. 18, 2024

Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a large and highly-integrated public chemical database resource at NIH. In the past two years, significant updates were made to PubChem. With additions from over 130 new sources, contains >1000 data 119 million compounds, 322 substances 295 bioactivities. New interfaces, such as consolidated literature panel patent knowledge panel, developed. The combines all references about compound into single list, allowing users easily find, sort, export relevant articles for in one place. panels given query or gene display chemicals, genes, diseases co-mentioned with documents, helping explore relationships between co-occurring entities within documents. PubChemRDF was expanded include co-occurrence underlying enabling exploit semantic web technologies entity based on co-occurrences scientific literature. usability accessibility of information chemicals non-discrete structures (e.g. biologics, minerals, polymers, UVCBs glycans) greatly improved dedicated pages that provide comprehensive view available these chemicals.

Язык: Английский

Процитировано

17
An atlas of protein-protein interactions across mouse tissues DOI Creative Commons
Michael A. Skinnider, Nichollas E. Scott,

Anna Prudova

и другие.

Cell, Год журнала: 2021, Номер 184(15), С. 4073 - 4089.e17

Опубликована: Июль 1, 2021

Язык: Английский

Процитировано

96
Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system DOI Creative Commons
Maria Y. Sachkova, Eva-Lena Nordmann, Joan J. Soto Àngel

и другие.

Current Biology, Год журнала: 2021, Номер 31(23), С. 5274 - 5285.e6

Опубликована: Сен. 28, 2021

Язык: Английский

Процитировано

80
JGI Plant Gene Atlas: an updateable transcriptome resource to improve functional gene descriptions across the plant kingdom DOI Creative Commons
Avinash Sreedasyam, Christopher Plott, Md Shakhawat Hossain

и другие.

Nucleic Acids Research, Год журнала: 2023, Номер 51(16), С. 8383 - 8401

Опубликована: Авг. 1, 2023

Abstract Gene functional descriptions offer a crucial line of evidence for candidate genes underlying trait variation. Conversely, plant responses to environmental cues represent important resources decipher gene function and subsequently provide molecular targets improvement through editing. However, biological roles large proportions across the phylogeny are poorly annotated. Here we describe Joint Genome Institute (JGI) Plant Atlas, an updateable data resource consisting transcript abundance assays spanning 18 diverse species. To integrate these genotypes, analyzed expression profiles, built clusters that exhibited tissue/condition specific expression, tested transcriptional response queues. We discovered extensive phylogenetically constrained condition-specific profiles without any previously documented annotation. Such conserved patterns tightly co-expressed let us assign derived additional information 64 495 with otherwise unknown functions. The ever-expanding Atlas is available at JGI (https://plantgeneatlas.jgi.doe.gov) Phytozome (https://phytozome.jgi.doe.gov/), providing bulk access user-specified queries sets. Combined, web interfaces users differentially expressed genes, track orthologs plants, graphically visualize ontology pathway enrichments.

Язык: Английский

Процитировано

36
The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species DOI Creative Commons
Tim Putman, Kevin Schaper, Nicolas Matentzoglu

и другие.

Nucleic Acids Research, Год журнала: 2023, Номер 52(D1), С. D938 - D949

Опубликована: Ноя. 24, 2023

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing ontologies, semantic models, knowledge graphs translational research. App an integrated platform combining about genes, phenotypes, diseases across species. Monarch's APIs enable access to carefully curated datasets advanced analysis tools that support disease diverse applications such as variant prioritization, deep phenotyping, patient profile-matching. We have migrated our system into scalable, cloud-based infrastructure; simplified ingestion graph integration systems; enhanced mapping standards; developed new user interface with novel search navigation features. Furthermore, we analytic customized plugin OpenAI's ChatGPT increase reliability its responses data, allowing us interrogate in using state-of-the-art Large Language Models. resources can be found monarchinitiative.org corresponding code repository github.com/monarch-initiative/monarch-app.

Язык: Английский

Процитировано

25