A Framework for Autonomous AI-Driven Drug Discovery DOI Creative Commons

Douglas W. Selinger,

Tom Wall,

Eleni Stylianou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The exponential increase in biomedical data offers unprecedented opportunities for drug discovery, yet overwhelms traditional analysis methods, limiting the pace of new development. Here we introduce a framework autonomous artificial intelligence (AI)-driven discovery that integrates knowledge graphs with large language models (LLMs). It is capable planning and carrying out automated programs while providing details its research strategy, progress, supporting points, enabling thorough assessment methods findings. At heart this lies “focal graph” - novel construct harnesses centrality algorithms to distill vast, noisy datasets into concise, transparent, data-driven hypotheses. By high-throughput search result interpretation, such could be used execute massive numbers searches, identify patterns across complex, diverse datasets, prioritize actionable hypotheses at scale speed unachievable by human researchers alone. We demonstrate even small- applications approach can yield novel, transparent insights relevant multiple stages process present prototype system autonomously executing multi-step target workflow. focal graph described here, automation it enables, represents promising path forward: towards deeper understanding mechanisms underlying disease true acceleration development therapeutics. Graphical

Language: Английский

Structure–function relationship of the brown seaweed Undaria pinnatifida laminaran: Protein kinase C-mediated mucus secretion and gut barrier restoration DOI
Kit‐Leong Cheong, Lin Chen, Siyuan Lu

et al.

Carbohydrate Polymers, Journal Year: 2025, Volume and Issue: unknown, P. 123525 - 123525

Published: March 1, 2025

Language: Английский

Citations

2
Temporal Transcriptomic Analysis of Periodontal Disease Progression and Its Molecular Links to Systemic Diseases DOI Open Access

Teerachate Nantakeeratipat,

Chiharu Fujihara, Masahide Takedachi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1998 - 1998

Published: Feb. 25, 2025

Periodontal disease, a prevalent oral inflammatory condition, is implicated in exacerbating systemic diseases. However, the molecular mechanisms underlying this association remain unclear. In study, we performed RNA sequencing of gingival tissue samples collected from mouse model periodontal disease at multiple time points to investigate dynamic transcriptomic changes during progression. Our analysis revealed distinct temporal gene expression patterns associated with key and immune response pathways. These findings suggest stepwise progression process, potentially contributing inflammation through shared signaling networks. We further identified specific genes pathways that may mediate bidirectional relationship between conditions such as cardiovascular diabetes. By elucidating dynamics study provides insights into pathogenesis its implications. It identifies potential biomarkers therapeutic targets for local management.

Language: Английский

Citations

0
Structure, Function, and Regulation of LytA: The N-Acetylmuramoyl-l-alanine Amidase Driving the “Suicidal Tendencies” of Streptococcus pneumoniae—A Review DOI Creative Commons
Ernesto Garcı́a

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 827 - 827

Published: April 5, 2025

Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for range of diseases from mild infections to invasive pneumococcal diseases, particularly affecting children, the elderly, and immunocompromised individuals. Despite conjugate vaccines having reduced disease incidence, challenges persist due serotype diversity, vaccine coverage gaps, antibiotic resistance. This review highlights role LytA, key autolysin (N-acetylmuramoyl-l-alanine amidase), in biology. LytA regulates autolysis, contributes inflammation, biofilm formation, impairs bacterial clearance. It also modulates complement activation, aiding immune evasion. expression influenced by environmental signals genetic regulation tied competence transformation, which an important virulence trait, meningitis. With increase resistance, has emerged as potential therapeutic target. Current research explores its use bacteriolytic therapies, development, synergistic strategies. Various compounds, including synthetic peptides, plant extracts, small molecules, have been investigated their ability trigger LytA-mediated lysis. Future directions include development novel anti-pneumococcal interventions leveraging LytA’s properties while overcoming efficacy resistance-related challenges. Human challenge models animal studies continue deepen our understanding pathogenesis treatment

Language: Английский

Citations

0
Construction and Influence of Induced Pluripotent Stem Cells on Early Embryo Development in Black Bone Sheep DOI Creative Commons
Daqing Wang, Yiyi Liu, Li Lu

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(5), P. 484 - 484

Published: April 28, 2025

The piggyBac+TET-on transposon induction system has a high efficiency in integrating exogenous genes multiple cell types, can precisely integrate to reduce genomic damage, flexible gene expression regulation, and strong genetic stability. When used conjunction with somatic nuclear transfer experiments, it effectively reveal the intrinsic mechanisms of early biological development. This study successfully reprogrammed black-boned sheep fibroblasts (SFs) into induced pluripotent stem cells (iPSCs) using investigated their impact on embryonic Seven reprogramming factors (bovine OCT4, SOX2, KLF4, cMyc, porcine NANOG, Lin-28, SV40 Large T) were delivered SFs, inducing iPSCs. A growth performance analysis revealed that iPSC clones exhibited raised or flat morphology clear edges, positive alkaline phosphatase staining, normal karyotypes. transcriptome indicated significant enrichment iPSCs oxidative phosphorylation proliferation pathways, an up-regulated ATP5B, SDHB, Bcl-2, CDK1, Cyclin D1 down-regulated BAX (p < 0.05). Somatic experiments demonstrated cleavage rate (85% ± 2.12) blastocyst (52% 2.11) significantly higher than those SFs detection trilineage marker confirmed levels endoderm (DCN, NANOS3, FOXA2, FOXD3, SOX17), mesoderm (KDR, CD34, NFH), ectoderm (NEUROD) markers 0.01). findings demonstrate possess pluripotency potential differentiate all three germ layers, revealing by which influence development providing critical foundation for research cells.

Language: Английский

Citations

0
DNA methylation modification: Dawn of research on cornea-related diseases DOI
Q. Pan,

Xiaoning Ge,

Di Wang

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123757 - 123757

Published: May 1, 2025

Language: Английский

Citations

0
A Framework for Autonomous AI-Driven Drug Discovery DOI Creative Commons

Douglas W. Selinger,

Tom Wall,

Eleni Stylianou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The exponential increase in biomedical data offers unprecedented opportunities for drug discovery, yet overwhelms traditional analysis methods, limiting the pace of new development. Here we introduce a framework autonomous artificial intelligence (AI)-driven discovery that integrates knowledge graphs with large language models (LLMs). It is capable planning and carrying out automated programs while providing details its research strategy, progress, supporting points, enabling thorough assessment methods findings. At heart this lies “focal graph” - novel construct harnesses centrality algorithms to distill vast, noisy datasets into concise, transparent, data-driven hypotheses. By high-throughput search result interpretation, such could be used execute massive numbers searches, identify patterns across complex, diverse datasets, prioritize actionable hypotheses at scale speed unachievable by human researchers alone. We demonstrate even small- applications approach can yield novel, transparent insights relevant multiple stages process present prototype system autonomously executing multi-step target workflow. focal graph described here, automation it enables, represents promising path forward: towards deeper understanding mechanisms underlying disease true acceleration development therapeutics. Graphical

Language: Английский

Citations

0