The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D638 - D646

Published: Nov. 12, 2022

Much of the complexity within cells arises from functional and regulatory interactions among proteins. The core these is increasingly known, but novel continue to be discovered, information remains scattered across different database resources, experimental modalities levels mechanistic detail. STRING (https://string-db.org/) systematically collects integrates protein-protein interactions-both physical as well associations. data originate a number sources: automated text mining scientific literature, computational interaction predictions co-expression, conserved genomic context, databases experiments known complexes/pathways curated sources. All are critically assessed, scored, subsequently automatically transferred less well-studied organisms using hierarchical orthology information. can accessed via website, also programmatically bulk downloads. most recent developments in (version 12.0) are: (i) it now possible create, browse analyze full network for any genome interest, by submitting its complement encoded proteins, (ii) co-expression channel uses variational auto-encoders predict interactions, covers two new sources, single-cell RNA-seq proteomics (iii) confidence each experimentally derived estimated based on detection method used, communicated user web-interface. Furthermore, continues enhance facilities enrichment analysis, which fully available user-submitted genomes.

Language: Английский

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From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 18, 2024

The revolution brought about by AlphaFold2 opens promising perspectives to unravel the complexity of protein-protein interaction networks. analysis networks obtained from proteomics experiments does not systematically provide delimitations regions. This is particular concern in case interactions mediated intrinsically disordered regions, which site generally small. Using a dataset protein-peptide complexes involving regions that are non-redundant with structures used training, we show when using full sequences proteins, AlphaFold2-Multimer only achieves 40% success rate identifying correct and structure interface. By delineating region into fragments decreasing size combining different strategies for integrating evolutionary information, manage raise this up 90%. We obtain similar rates much larger protein taken ELM database. Beyond identification site, our study also explores specificity issues. advantages limitations confidence score discriminate between alternative binding partners, task can be particularly challenging small motifs.

Language: Английский

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Construction and Application of Nanozyme Sensor Arrays

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(21), P. 8221 - 8233

Published: May 13, 2024

Compared with traditional "lock–key mode" biosensors, a sensor array consists of series sensing elements based on intermolecular interactions (typically hydrogen bonds, van der Waals forces, and electrostatic interactions). At the same time, arrays also have advantages fast response, high sensitivity, low energy consumption, cost, rich output signals, imageability, which attracted widespread attention from researchers. Nanozymes are nanomaterials own enzyme-like properties. Because adjustable activity, stability, cost effectiveness nanozymes, they potential candidates for construction to different signals analytes through chemoresponse colorants, solves shortcomings sensors that cannot support multiple detection lack universality. Recently, nanozymes as nonspecific recognition receptors has much more researchers been applied precise proteins, bacteria, heavy metals. In this perspective, is given regulation their activity. Particularly, building principles methods analyzed, applications summarized. Finally, approaches overcome challenges perspectives presented analyzed facilitating further research development nanozyme arrays. This perspective should be helpful gaining insight into ideas within field

Language: Английский

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Proteomics: An In‐Depth Review on Recent Technical Advances and Their Applications in Biomedicine

Medicinal Research Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

ABSTRACT Proteins hold pivotal importance since many diseases manifest changes in protein activity. Proteomics techniques provide a comprehensive exploration of structure, abundance, and function biological samples, enabling the holistic characterization overall organisms. Nowadays, breadth emerging methodologies proteomics is unprecedentedly vast, with constant optimization technologies sample processing, data collection, analysis, its scope application steadily transitioning from bench to clinic. Here, we offer an insightful review technical developments applications biomedicine over past 5 years. We focus on profound contributions profiling disease spectra, discovering new biomarkers, identifying promising drug targets, deciphering alterations conformation, unearthing protein–protein interactions. Moreover, summarize cutting‐edge potential breakthroughs pipeline principal challenges proteomics. Based these, aspire broaden applicability inspire researchers enhance our understanding complex systems by utilizing such techniques.

Language: Английский

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From single- to multi-omics: future research trends in medicinal plants

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 24(1)

Published: Nov. 22, 2022

Abstract Medicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies medicinal performed to identify molecular markers species functional genes controlling key biological traits, as well understand biosynthetic pathways bioactive regulatory mechanisms environmental responses. Omics technologies applied plants, including taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics mutagenomics. However, because complex regulation network, single usually fail explain specific phenomena. In recent years, reports integrated multi-omics increased. Until now, there few assessments developments upcoming trends in plants. We highlight research summarise typical bioinformatics resources available for analysing datasets, discuss related future directions challenges. This information facilitates further refinement current approaches leads new ideas.

Language: Английский

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From interaction networks to interfaces: Scanning intrinsically disordered regions using AlphaFold2

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 25, 2023

Abstract The revolution brought about by AlphaFold2 and the performance of AlphaFold2-Multimer open promising perspectives to unravel complexity protein-protein interaction networks. Nevertheless, analysis networks obtained from proteomics experiments does not systematically provide delimitations regions. This is particular concern in case interactions mediated intrinsically disordered regions, which site generally small. Using a dataset protein-peptide complexes involving protein regions that are non-redundant with structures used training, we show when using full sequences proteins involved networks, only achieves 40% success rate identifying correct structure interface. By delineating region into fragments decreasing size combining different strategies for integrating evolutionary information, managed raise this up 90%. Beyond identification site, our study also explores specificity issues. We advantages limitations confidence score discriminate between alternative binding partners, task can be particularly challenging small motifs.

Language: Английский

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Enantioselective effects of chiral profenofos on the conformation for human serum albumin

Pesticide Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 205, P. 106159 - 106159

Published: Sept. 30, 2024

Language: Английский

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Causal associations between circulating protein ratios and drug resistance in papillary thyroid cancer: a Mendelian randomization study

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 4, 2025

Circulating protein level ratios (CPLRs) may play a crucial role in tumor progression and drug resistance by mediating interactions within the microenvironment. This study aims to investigate causal associations between CPLRs papillary thyroid cancer (PTC), focusing on their potential implications mechanisms. Genetic data for 2821 were obtained from GWAS FinnGen databases. Mendelian randomization (MR) analysis, using inverse variance weighting (IVW) as primary method, was conducted explore causality. Sensitivity analyses, including heterogeneity pleiotropy tests, performed ensure robustness of results. Twelve identified causally associated with PTC. Seven CPLRs, such REG1A/TFF3 LAT/SPARC, reduced PTC risk, potentially reflecting protective In contrast, five MAD1L1/PSIP1 CIAPIN1/TYMP, linked increased suggesting promoting resistance. Reverse MR analysis revealed no significant associations, reinforcing directionality these findings. These findings highlight relevance pathogenesis PTC, providing insights into biomarkers therapeutic targets. Future research could focus translating strategies personalized medicine targeted treatment.

Language: Английский

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Establishing cryptic enzyme interactomes

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 277 - 297

Published: Jan. 1, 2025

Language: Английский

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PPIscreenML: Structure-based screening for protein-protein interactions using AlphaFold

Published: July 8, 2024

Protein-protein interactions underlie nearly all cellular processes. With the advent of protein structure prediction methods such as AlphaFold2 (AF2), models specific pairs can be built extremely accurately in most cases. However, determining relevance a given pair remains an open question. It is presently unclear how to use best structure-based tools infer whether candidate proteins indeed interact with one another: ideally, might even information screen amongst pairings build up interaction networks. Whereas for evaluating quality modeled complexes have been co-opted which (e.g., pDockQ and iPTM), there no rigorously benchmarked this task. Here we introduce PPIscreenML, classification model trained distinguish AF2 interacting from compelling decoy pairings. We find that PPIscreenML out-performs iPTM task, further exhibits impressive performance when identifying ligand/receptor engage another across structurally conserved tumor necrosis factor superfamily (TNFSF). Analysis benchmark results using not seen development strongly suggest generalizes beyond training data, making it broadly applicable new based on structural AF2.

Language: Английский

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