Molecular Systems Biology最新文献

Metabolic reaction fluxes as amplifiers and buffers of risk alleles for coronary artery disease.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-02 DOI: 10.1038/s44320-025-00097-2

Carles Foguet, Xilin Jiang, Scott C Ritchie, Elodie Persyn, Yu Xu, Chief Ben-Eghan, Henry J Taylor, Emanuele Di Angelantonio, John Danesh, Adam S Butterworth, Samuel A Lambert, Michael Inouye

{"title":"Metabolic reaction fluxes as amplifiers and buffers of risk alleles for coronary artery disease.","authors":"Carles Foguet, Xilin Jiang, Scott C Ritchie, Elodie Persyn, Yu Xu, Chief Ben-Eghan, Henry J Taylor, Emanuele Di Angelantonio, John Danesh, Adam S Butterworth, Samuel A Lambert, Michael Inouye","doi":"10.1038/s44320-025-00097-2","DOIUrl":"10.1038/s44320-025-00097-2","url":null,"abstract":"Genome-wide association studies have identified thousands of variants associated with disease risk but the mechanism by which such variants contribute to disease remains largely unknown. Indeed, a major challenge is that variants do not act in isolation but rather in the framework of highly complex biological networks, such as the human metabolic network, which can amplify or buffer the effect of specific risk alleles on disease susceptibility. Here we use genetically predicted reaction fluxes to perform a systematic search for metabolic fluxes acting as buffers or amplifiers of coronary artery disease (CAD) risk alleles. Our analysis identifies 30 risk locus-reaction flux pairs with significant interaction on CAD susceptibility involving 18 individual reaction fluxes and 8 independent risk loci. Notably, many of these reactions are linked to processes with putative roles in the disease such as the metabolism of inflammatory mediators. In summary, this work establishes proof of concept that biochemical reaction fluxes can have non-additive effects with risk alleles and provides novel insights into the interplay between metabolism and genetic variation on disease susceptibility.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circadian clock features define novel subtypes among breast cancer cells and shape drug sensitivity.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-02-24 DOI: 10.1038/s44320-025-00092-7

Carolin Ector, Jeff Didier, Sébastien De Landtsheer, Malthe S Nordentoft, Christoph Schmal, Ulrich Keilholz, Hanspeter Herzel, Achim Kramer, Thomas Sauter, Adrián E Granada

{"title":"Circadian clock features define novel subtypes among breast cancer cells and shape drug sensitivity.","authors":"Carolin Ector, Jeff Didier, Sébastien De Landtsheer, Malthe S Nordentoft, Christoph Schmal, Ulrich Keilholz, Hanspeter Herzel, Achim Kramer, Thomas Sauter, Adrián E Granada","doi":"10.1038/s44320-025-00092-7","DOIUrl":"10.1038/s44320-025-00092-7","url":null,"abstract":"The circadian clock regulates key physiological processes, including cellular responses to DNA damage. Circadian-based therapeutic strategies optimize treatment timing to enhance drug efficacy and minimize side effects, offering potential for precision cancer treatment. However, applying these strategies in cancer remains limited due to a lack of understanding of the clock's function across cancer types and incomplete insights into how the circadian clock affects drug responses. To address this, we conducted deep circadian phenotyping across a panel of breast cancer cell lines. Observing diverse circadian dynamics, we characterized metrics to assess circadian rhythm strength and stability in vitro. This led to the identification of four distinct circadian-based phenotypes among 14 breast cancer cell models: functional, weak, unstable, and dysfunctional clocks. Furthermore, we demonstrate that the circadian clock plays a critical role in shaping pharmacological responses to various anti-cancer drugs and we identify circadian features descriptive of drug sensitivity. Collectively, our findings establish a foundation for implementing circadian-based treatment strategies in breast cancer, leveraging clock phenotypes and drug sensitivity patterns to optimize therapeutic outcomes.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"315-340"},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-03-25 DOI: 10.1038/s44320-025-00093-6

Alexander Simonis, Sebastian J Theobald, Anna E Koch, Ram Mummadavarapu, Julie M Mudler, Andromachi Pouikli, Ulrike Göbel, Richard Acton, Sandra Winter, Alexandra Albus, Dmitriy Holzmann, Marie-Christine Albert, Michael Hallek, Henning Walczak, Thomas Ulas, Manuel Koch, Peter Tessarz, Robert Hänsel-Hertsch, Jan Rybniker

{"title":"Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.","authors":"Alexander Simonis, Sebastian J Theobald, Anna E Koch, Ram Mummadavarapu, Julie M Mudler, Andromachi Pouikli, Ulrike Göbel, Richard Acton, Sandra Winter, Alexandra Albus, Dmitriy Holzmann, Marie-Christine Albert, Michael Hallek, Henning Walczak, Thomas Ulas, Manuel Koch, Peter Tessarz, Robert Hänsel-Hertsch, Jan Rybniker","doi":"10.1038/s44320-025-00093-6","DOIUrl":"10.1038/s44320-025-00093-6","url":null,"abstract":"Immune memory plays a critical role in the development of durable antimicrobial immune responses. How precisely mRNA vaccines train innate immune cells to shape protective host defense mechanisms remains unknown. Here we show that SARS-CoV-2 mRNA vaccination significantly establishes histone H3 lysine 27 acetylation (H3K27ac) at promoters of human monocyte-derived macrophages, suggesting epigenetic memory. However, we found that two consecutive vaccinations were required for the persistence of H3K27ac, which matched with pro-inflammatory innate immune-associated transcriptional changes and antigen-mediated cytokine secretion. H3K27ac at promoter regions were preserved for six months and a single mRNA booster vaccine potently restored their levels and release of macrophage-derived cytokines. Interestingly, we found that H3K27ac at promoters is enriched for G-quadruplex DNA secondary structure-forming sequences in macrophage-derived nucleosome-depleted regions, linking epigenetic memory to nucleic acid structure. Collectively, these findings reveal that mRNA vaccines induce a highly dynamic and persistent training of innate immune cells enabling a sustained pro-inflammatory immune response.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"341-360"},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pulsed stimuli enable p53 phase resetting to synchronize single cells and modulate cell fate.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-03-03 DOI: 10.1038/s44320-025-00091-8

Harish Venkatachalapathy, Samuel Dallon, Zhilin Yang, Samira M Azarin, Casim A Sarkar, Eric Batchelor

{"title":"Pulsed stimuli enable p53 phase resetting to synchronize single cells and modulate cell fate.","authors":"Harish Venkatachalapathy, Samuel Dallon, Zhilin Yang, Samira M Azarin, Casim A Sarkar, Eric Batchelor","doi":"10.1038/s44320-025-00091-8","DOIUrl":"10.1038/s44320-025-00091-8","url":null,"abstract":"Oscillatory p53 expression occurs in individual cells responding to DNA breaks. While the majority of cells exhibit the same qualitative response, quantitative features of the oscillations (e.g., amplitude or period) can be highly variable between cells, generating heterogeneity in downstream cell fate responses. Since heterogeneity can be detrimental to therapies based on DNA damage, methods to induce synchronization of p53 oscillations across cells in a population have the potential to generate more predictable responses to DNA-damaging treatments. Using mathematical modeling and time-lapse microscopy, we demonstrated that p53 oscillations can be synchronized through the phenomenon of phase resetting. Surprisingly, p53 oscillations were synchronized over a wider range of damage-induction frequencies than predicted computationally. Recapitulating the range of synchronizing frequencies required, non-intuitively, a less robust oscillator. We showed that p53 phase resetting altered the expression of downstream targets responsible for cell fate depending on target mRNA stability. This study demonstrates that p53 oscillations can be phase reset and highlights the potential of driving p53 dynamics to reduce cellular variability and synchronize cell fate responses to DNA damage.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"390-412"},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abundant clock proteins point to missing molecular regulation in the plant circadian clock. 丰富的时钟蛋白表明植物昼夜节律时钟中缺少分子调控。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-02-20 DOI: 10.1038/s44320-025-00086-5

Uriel Urquiza-García, Nacho Molina, Karen J Halliday, Andrew J Millar

{"title":"Abundant clock proteins point to missing molecular regulation in the plant circadian clock.","authors":"Uriel Urquiza-García, Nacho Molina, Karen J Halliday, Andrew J Millar","doi":"10.1038/s44320-025-00086-5","DOIUrl":"10.1038/s44320-025-00086-5","url":null,"abstract":"Understanding the biochemistry behind whole-organism traits such as flowering time is a longstanding challenge, where mathematical models are critical. Very few models of plant gene circuits use the absolute units required for comparison to biochemical data. We refactor two detailed models of the plant circadian clock from relative to absolute units. Using absolute RNA quantification, a simple model predicted abundant clock protein levels in Arabidopsis thaliana, up to 100,000 proteins per cell. NanoLUC reporter protein fusions validated the predicted levels of clock proteins in vivo. Recalibrating the detailed models to these protein levels estimated their DNA-binding dissociation constants (Kd). We estimate the same Kd from multiple results in vitro, extending the method to any promoter sequence. The detailed models simulated the Kd range estimated from LUX DNA-binding in vitro but departed from the data for CCA1 binding, pointing to further circadian mechanisms. Our analytical and experimental methods should transfer to understand other plant gene regulatory networks, potentially including the natural sequence variation that contributes to evolutionary adaptation.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"361-389"},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 DOI: 10.1038/s44320-025-00096-3

Joshua L Justice, Todd M Greco, Josiah E Hutton, Tavis J Reed, Megan L Mair, Juan Botas, Ileana M Cristea

{"title":"Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.","authors":"Joshua L Justice, Todd M Greco, Josiah E Hutton, Tavis J Reed, Megan L Mair, Juan Botas, Ileana M Cristea","doi":"10.1038/s44320-025-00096-3","DOIUrl":"10.1038/s44320-025-00096-3","url":null,"abstract":"Huntington's disease (HD) is a debilitating neurodegenerative disorder affecting an individual's cognitive and motor abilities. HD is caused by a mutation in the huntingtin gene producing a toxic polyglutamine-expanded protein (mHTT) and leading to degeneration in the striatum and cortex. Yet, the molecular signatures that underlie tissue-specific vulnerabilities remain unclear. Here, we investigate this aspect by leveraging multi-epitope protein interaction assays, subcellular fractionation, thermal proteome profiling, and genetic modifier assays. The use of human cell, mouse, and fly models afforded capture of distinct subcellular pools of epitope-enriched and tissue-dependent interactions linked to dysregulated cellular pathways and disease relevance. We established an HTT association with nearly all subunits of the transcriptional regulatory Mediator complex (20/26), with preferential enrichment of MED15 in the tail domain. Using HD and KO models, we find HTT modulates the subcellular localization and assembly of the Mediator. We demonstrated striatal enriched and functional interactions with regulators of calcium homeostasis and chromatin remodeling, whose disease relevance was supported by HD fly genetic modifiers assays. Altogether, we offer insights into tissue- and localization-dependent (m)HTT functions and pathobiology.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced flux potential analysis links changes in enzyme expression to metabolic flux.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI: 10.1038/s44320-025-00090-9

Xuhang Li, Albertha J M Walhout, L Safak Yilmaz

{"title":"Enhanced flux potential analysis links changes in enzyme expression to metabolic flux.","authors":"Xuhang Li, Albertha J M Walhout, L Safak Yilmaz","doi":"10.1038/s44320-025-00090-9","DOIUrl":"10.1038/s44320-025-00090-9","url":null,"abstract":"Algorithms that constrain metabolic network models with enzyme levels to predict metabolic activity assume that changes in enzyme levels are indicative of flux variations. However, metabolic flux can also be regulated by other mechanisms such as allostery and mass action. To systematically explore the relationship between fluctuations in enzyme expression and flux, we combine available yeast proteomic and fluxomic data to reveal that flux changes can be best predicted from changes in enzyme levels of pathways, rather than the whole network or only cognate reactions. We implement this principle in an 'enhanced flux potential analysis' (eFPA) algorithm that integrates enzyme expression data with metabolic network architecture to predict relative flux levels of reactions including those regulated by other mechanisms. Applied to human data, eFPA consistently predicts tissue metabolic function using either proteomic or transcriptomic data. Additionally, eFPA efficiently handles data sparsity and noisiness, generating robust flux predictions with single-cell gene expression data. Our approach outperforms alternatives by striking an optimal balance, evaluating enzyme expression at pathway level, rather than either single-reaction or whole-network levels.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"413-445"},"PeriodicalIF":8.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mouse promoters are characterised by low occupancy and high turnover of RNA polymerase II.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-03-31 DOI: 10.1038/s44320-025-00094-5

Kasit Chatsirisupachai, Christina J I Moene, Rozemarijn Kleinendorst, Elisa Kreibich, Nacho Molina, Arnaud Krebs

{"title":"Mouse promoters are characterised by low occupancy and high turnover of RNA polymerase II.","authors":"Kasit Chatsirisupachai, Christina J I Moene, Rozemarijn Kleinendorst, Elisa Kreibich, Nacho Molina, Arnaud Krebs","doi":"10.1038/s44320-025-00094-5","DOIUrl":"10.1038/s44320-025-00094-5","url":null,"abstract":"The general transcription machinery and its occupancy at promoters are highly conserved across metazoans. This contrasts with the kinetics of mRNA production that considerably differ between model species such as Drosophila and mouse. The molecular basis for these kinetic differences is currently unknown. Here, we used Single-Molecule Footprinting to measure RNA Polymerase II (Pol II) occupancy, the fraction of DNA molecules bound, at promoters in mouse and Drosophila cell lines. Single-molecule data reveals that Pol II occupancy is on average 3-5 times more frequent at transcriptionally active Drosophila promoters than active mouse promoters. Kinetic modelling of the occupancy states suggests that these differences in Pol II occupancy are determined by the ratio between the transcription initiation and Pol II turnover rates. We used chemical perturbation of transcription initiation to determine Pol II turnover rate in both species. Integration of these data into the model shows that infrequent Pol II occupancy in mouse is explained by the combination of high Pol II turnover and low transcription initiation rates.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response. 吉西他滨和ATR抑制剂通过阻断DNA损伤反应协同杀死PDAC细胞。

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1038/s44320-025-00085-6

Stefanie Höfer, Larissa Frasch, Sarah Brajkovic, Kerstin Putzker, Joe Lewis, Hendrik Schürmann, Valentina Leone, Amirhossein Sakhteman, Matthew The, Florian P Bayer, Julian Müller, Firas Hamood, Jens T Siveke, Maximilian Reichert, Bernhard Kuster

{"title":"Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.","authors":"Stefanie Höfer, Larissa Frasch, Sarah Brajkovic, Kerstin Putzker, Joe Lewis, Hendrik Schürmann, Valentina Leone, Amirhossein Sakhteman, Matthew The, Florian P Bayer, Julian Müller, Firas Hamood, Jens T Siveke, Maximilian Reichert, Bernhard Kuster","doi":"10.1038/s44320-025-00085-6","DOIUrl":"10.1038/s44320-025-00085-6","url":null,"abstract":"The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway, including phosphorylated pS468 of CHEK1, as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"231-253"},"PeriodicalIF":8.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveraging prior knowledge to infer gene regulatory networks from single-cell RNA-sequencing data.

IF 8.5 1区生物学

Molecular Systems Biology Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.1038/s44320-025-00088-3

Marco Stock, Corinna Losert, Matteo Zambon, Niclas Popp, Gabriele Lubatti, Eva Hörmanseder, Matthias Heinig, Antonio Scialdone

{"title":"Leveraging prior knowledge to infer gene regulatory networks from single-cell RNA-sequencing data.","authors":"Marco Stock, Corinna Losert, Matteo Zambon, Niclas Popp, Gabriele Lubatti, Eva Hörmanseder, Matthias Heinig, Antonio Scialdone","doi":"10.1038/s44320-025-00088-3","DOIUrl":"10.1038/s44320-025-00088-3","url":null,"abstract":"Many studies have used single-cell RNA sequencing (scRNA-seq) to infer gene regulatory networks (GRNs), which are crucial for understanding complex cellular regulation. However, the inherent noise and sparsity of scRNA-seq data present significant challenges to accurate GRN inference. This review explores one promising approach that has been proposed to address these challenges: integrating prior knowledge into the inference process to enhance the reliability of the inferred networks. We categorize common types of prior knowledge, such as experimental data and curated databases, and discuss methods for representing priors, particularly through graph structures. In addition, we classify recent GRN inference algorithms based on their ability to incorporate these priors and assess their performance in different contexts. Finally, we propose a standardized benchmarking framework to evaluate algorithms more fairly, ensuring biologically meaningful comparisons. This review provides guidance for researchers selecting GRN inference methods and offers insights for developers looking to improve current approaches and foster innovation in the field.","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"214-230"},"PeriodicalIF":8.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0