PLoS Genetics最新文献

{"title":"Germline mutation rates and fine-scale recombination parameters in zebra finch.","authors":"Djivan Prentout, Daria Bykova, Carla Hoge, Daniel M Hooper, Callum S McDiarmid, Felix Wu, Simon C Griffith, Marc de Manuel, Molly Przeworski","doi":"10.1371/journal.pgen.1011661","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011661","url":null,"abstract":"<p><p>Most of our understanding of the fundamental processes of mutation and recombination stems from a handful of disparate model organisms and pedigree studies of mammals, with little known about other vertebrates. To gain a broader comparative perspective, we focused on the zebra finch (Taeniopygia castanotis), which, like other birds, differs from mammals in its karyotype (which includes many micro-chromosomes), in the mechanism by which recombination is directed to the genome, and in aspects of ontogenesis. We collected genome sequences from three generation pedigrees that provide information about 80 meioses, inferring 202 single-point de novo mutations, 1,088 crossovers, and 275 non-crossovers. On that basis, we estimated a sex-averaged mutation rate of 5.0 × 10-9 per base pair per generation, on par with mammals that have a similar generation time (~2-3 years). Also as in mammals, we found a paternal germline mutation bias at later stages of gametogenesis (of 1.7:1) but no discernible difference between sexes in early development. Examining recombination patterns, we found that the sex-averaged crossover rate on macro-chromosomes is 0.93 cM/Mb, with a pronounced enrichment of crossovers near telomeres. In contrast, non-crossover rates are more uniformly distributed. On micro-chromosomes, sex-averaged crossover rates are substantially higher (3.96 cM/Mb), in accordance with crossover homeostasis, and both crossover and non-crossover events are more uniformly distributed. At a finer scale, recombination events overlap CpG islands more often than expected by chance, as expected in the absence of PRDM9. Estimates of the degree of GC-biased gene conversion (59%), the mean non-crossover conversion tract length (~32 bp), and the non-crossover-to-crossover ratio (5.4:1) are all comparable to those reported in primates and mice. Therefore, properties of germline mutation and recombination resolutions remain similar over large phylogenetic distances.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011661"},"PeriodicalIF":4.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of quantitative trait loci (QTLs) for key cheese making phenotypes in the blue-cheese mold Penicillium roqueforti.","authors":"Thibault Caron, Ewen Crequer, Mélanie Le Piver, Stéphanie Le Prieur, Sammy Brunel, Alodie Snirc, Gwennina Cueff, Daniel Roueyre, Michel Place, Christophe Chassard, Adeline Simon, Ricardo C Rodríguez de la Vega, Monika Coton, Emmanuel Coton, Marie Foulongne-Oriol, Antoine Branca, Tatiana Giraud","doi":"10.1371/journal.pgen.1011669","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011669","url":null,"abstract":"<p><p>Elucidating the genomic architecture of quantitative traits is essential for our understanding of adaptation and for breeding in domesticated organisms. Penicillium roqueforti is the mold used worldwide for the blue cheese maturation, contributing to flavors through proteolytic and lipolytic activities. The two domesticated cheese populations display very little genetic diversity, but are differentiated and carry opposite mating types. We produced haploid F1 progenies from five crosses, using parents belonging to cheese and non-cheese populations. Analyses of high-quality genome assemblies of the parental strains revealed five large translocations, two having occurred via a circular intermediate, one with footprints of Starship giant mobile elements. Offspring genotyping with genotype-by-sequencing (GBS) revealed several genomic regions with segregation distortion, possibly linked to degeneration in cheese lineages. We found transgressions for several traits relevant for cheese making, with offspring having more extreme trait values than parental strains. We identified quantitative trait loci (QTLs) for colony color, lipolysis, proteolysis, extrolite production, including mycotoxins, but not for growth rates. Some genomic regions appeared rich in QTLs for both lipid and protein metabolism, and other regions for the production of multiple extrolites, indicating that QTLs have pleiotropic effects. Some QTLs corresponded to known biosynthetic gene clusters, e.g., for the production of melanin or extrolites. F1 hybrids constitute valuable strains for cheese producers, with new traits and new allelic combinations, and allowed identifying target genomic regions for traits important in cheese making, paving the way for strain improvement. The findings further contribute to our understanding of the genetic mechanisms underlying rapid adaptation, revealing convergent adaptation targeting major gene regulators.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011669"},"PeriodicalIF":4.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YebC2 resolves ribosome stalling and increases fitness of cells lacking EF-P and the ABCF ATPase YfmR.","authors":"Hye-Rim Hong, Cassidy R Prince, Letian Wu, Isabella N Lin, Katrina Callan, Heather A Feaga","doi":"10.1371/journal.pgen.1011633","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011633","url":null,"abstract":"<p><p>Ribosome stalling is a major source of cellular stress. Therefore, many specialized elongation factors help prevent ribosome stalling. One of the best characterized of these factors is EF-P, which prevents ribosome stalling at polyproline tracts and other difficult-to-translate sequences. Recent evidence suggests that other factors also facilitate translation of polyproline motifs. For example, YfmR was recently identified as a protein that prevents ribosome stalling at proline-containing sequences in the absence of EF-P. Here, we show that YebC2 (formerly YeeI) functions as a translation factor in Bacillus subtilis that resolves ribosome stalling at polyprolines. YebC2 associates with the ribosome, supporting a direct role for YebC2 in translation. Moreover, YebC2 can reduce ribosome stalling and support cellular fitness in the absence of EF-P and YfmR. Finally, we present evidence that YebC2 is evolutionarily distinct from previously characterized YebC-family transcription factors and demonstrate that these paralogs have distinct physiological roles in B. subtilis. Altogether our work identifies YebC2 as a translation factor that resolves ribosome stalling in B. subtilis and provides crucial insight into the relationship between YebC2, EF-P, and YfmR, three factors that prevent ribosome stalling at polyprolines.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011633"},"PeriodicalIF":4.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11990639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep-time gene expression shift reveals an ancient change in avian muscle phenotypes.","authors":"Christina M Harvey, Matthew J Fuxjager, James B Pease","doi":"10.1371/journal.pgen.1011663","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011663","url":null,"abstract":"<p><p>Gene duplication is an important process of molecular evolutionary change, though identifying these events and their functional implications remains challenging. Studies on gene duplication more often focus on the presence of paralogous genes within the genomes and less frequently explore shifts in expression. We investigated the evolutionary history of calsequestrin (CASQ), a crucial calcium-binding protein in the junctional sarcoplasmic reticulum of muscle tissues. CASQ exists in jawed vertebrates as subfunctionalized paralogs CASQ1 and CASQ2 expressed primarily in skeletal and cardiac muscles, respectively. We used an enhanced sequence dataset to support initial duplication of CASQl in a jawed fish ancestor prior to the divergence of cartilaginous fishes. Surprisingly, we find CASQ2 is the predominant skeletal muscle paralog in birds, while CASQ1 is either absent or effectively nonfunctional. Changes in the amino acid composition and electronegativity of avian CASQ2 suggest enhancement to calcium-binding properties that preceded the loss of CASQ1. We identify this phenomenon as CASQ2 \"synfunctionalization,\" where one paralog functionally replaces another. While additional studies are needed to fully understand the dynamics of CASQ1 and CASQ2 in bird muscles, the long and consistent history of CASQ subfunctions outside of birds indicate a substantial evolutionary pressure on calcium-cycling processes in muscle tissues, likely connected to increased avian cardiovascular and metabolic demands. Our study provides an important insight into the molecular evolution of birds and shows how gene expression patterns can be comparatively studied across phylum-scale deep time to reveal key evolutionary events.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011663"},"PeriodicalIF":4.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular basis of the genetic correlation between body mass index and brain morphological traits.","authors":"Daniela Fusco, Camilla Marinelli, Mathilde André, Lucia Troiani, Martina Noè, Fabrizio Pizzagalli, Davide Marnetto, Paolo Provero","doi":"10.1371/journal.pgen.1011658","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011658","url":null,"abstract":"<p><p>Several studies have demonstrated significant phenotypic and genetic correlations between body mass index (BMI) and brain morphological traits derived from structural magnetic resonance imaging (sMRI). We use the sMRI, BMI, and genetic data collected by the UK Biobank to systematically compute the genetic correlations between area, volume, and thickness measurements of hundreds of brain structures on one hand, and BMI on the other. In agreement with previous literature, we find many such measurements to have negative genetic correlation with BMI. We then dissect the molecular mechanisms underlying such correlations using brain eQTL data and summary-based Mendelian randomization, thus producing an atlas of genes whose genetically regulated expression in brain tissues is pleiotropic with brain morphology and BMI. Fine-mapping followed by colocalization analysis allows, in several cases, the identification of credible sets of variants likely to be causal for both the macroscopic phenotypes and for gene expression. In particular, epigenetic fine mapping identifies variant rs7187776 in the 5' UTR of the TUFM gene as likely to be causal of increased BMI and decreased caudate volume, possibly through the creation, by the alternate allele, of an ETS binding site leading to increased chromatin accessibility, specifically in microglial cells.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011658"},"PeriodicalIF":4.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic regions of current low hybridisation mark long-term barriers to gene flow in scarce swallowtail butterflies.","authors":"Sam Ebdon, Dominik R Laetsch, Roger Vila, Stuart J E Baird, Konrad Lohse","doi":"10.1371/journal.pgen.1011655","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011655","url":null,"abstract":"<p><p>Many closely related species continue to hybridise after millions of generations of divergence. However, the extent to which current patterning in hybrid zones connects back to the speciation process remains unclear: does evidence for current multilocus barriers support the hypothesis of speciation due to multilocus divergence? We analyse whole-genome sequencing data to investigate the speciation history of the scarce swallowtails Iphiclidespodalirius and I . feisthamelii, which abut at a narrow ( ∼ 25 km) contact zone north of the Pyrenees. We first quantify the heterogeneity of effective migration rate under a model of isolation with migration, using genomes sampled across the range to identify long-term barriers to gene flow. Secondly, we investigate the recent ancestry of individuals from the hybrid zone using genome polarisation and estimate the coupling coefficient under a model of a multilocus barrier. We infer a low rate of long-term gene flow from I . feisthamelii into I . podalirius - the direction of which matches the admixture across the hybrid zone - and complete reproductive isolation across  ≈  33% of the genome. Our contrast of recent and long-term gene flow shows that regions of low recent hybridisation are indeed enriched for long-term barriers which maintain divergence between these hybridising sister species. This finding paves the way for future analysis of the evolution of reproductive isolation along the speciation continuum.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011655"},"PeriodicalIF":4.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing nonlinear transcriptome- and proteome-wide association studies via trait imputation with applications to Alzheimer's disease.","authors":"Ruoyu He, Jingchen Ren, Mykhaylo M Malakhov, Wei Pan","doi":"10.1371/journal.pgen.1011659","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011659","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) performed on large cohort and biobank datasets have identified many genetic loci associated with Alzheimer's disease (AD). However, the younger demographic of biobank participants relative to the typical age of late-onset AD has resulted in an insufficient number of AD cases, limiting the statistical power of GWAS and any downstream analyses. To mitigate this limitation, several trait imputation methods have been proposed to impute the expected future AD status of individuals who may not have yet developed the disease. This paper explores the use of imputed AD status in nonlinear transcriptome/proteome-wide association studies (TWAS/PWAS) to identify genes and proteins whose genetically regulated expression is associated with AD risk. In particular, we considered the TWAS/PWAS method DeLIVR, which utilizes deep learning to model the nonlinear effects of expression on disease. We trained transcriptome and proteome imputation models for DeLIVR on data from the Genotype-Tissue Expression (GTEx) Project and the UK Biobank (UKB), respectively, with imputed AD status in UKB participants as the outcome. Next, we performed hypothesis testing for the DeLIVR models using clinically diagnosed AD cases from the Alzheimer's Disease Sequencing Project (ADSP). Our results demonstrate that nonlinear TWAS/PWAS trained with imputed AD outcomes successfully identifies known and putative AD risk genes and proteins. Notably, we found that training with imputed outcomes can increase statistical power without inflating false positives, enabling the discovery of molecular exposures with potentially nonlinear effects on neurodegeneration.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011659"},"PeriodicalIF":4.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk.","authors":"Claire Liefferinckx, David Stern, Hélène Perée, Jérémie Bottieau, Alice Mayer, Christophe Dubussy, Eric Quertinmont, Vjola Tafciu, Charlotte Minsart, Vyacheslav Petrov, Alex Kvasz, Wouter Coppieters, Latifa Karim, Souad Rahmouni, Michel Georges, Denis Franchimont","doi":"10.1371/journal.pgen.1011599","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011599","url":null,"abstract":"<p><p>Hundreds of risk loci for immune mediated inflammatory and infectious diseases have been identified by genome-wide association studies (GWAS). Yet, what causal variants and genes in risk loci underpin the observed associations remains poorly understood for most. The identification of colocalized cis-expression Quantitative Trait Loci (cis-eQTLs) is a promising way to identify candidate causative genes. The catalogue of cis-eQTLs of the immune system is likely incomplete as many cis-eQTLs may be context-specific. We built a large cohort of 406 healthy individuals and expanded the immune cis-regulome through their whole blood transcriptome obtained after stimulation with specific toll-like receptor (TLR) agonists and T-cell receptor (TCR) antagonist. We report three mechanisms that may explain why an eQTL could only be revealed after immune stimulation. More than half of the cis-eQTLs detected in this study would have been overlooked without specific immune stimulations. We then mined this new catalogue of response (r)eQTLs, with public GWAS summary statistics of three diseases through a colocalization approach: inflammatory bowel diseases, rheumatoid arthritis and COVID-19 disease. We identified reQTL-specific colocalizations for risk loci for which no matching eQTL were reported before, revealing interesting new candidate causal genes.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011599"},"PeriodicalIF":4.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Condensin IDC, DPY-21, and CEC-4 maintain X chromosome repression in C. elegans.","authors":"Jessica Trombley, Audry I Rakozy, Christian A McClear, Eshna Jash, Györgyi Csankovszki","doi":"10.1371/journal.pgen.1011247","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011247","url":null,"abstract":"<p><p>Dosage compensation in Caenorhabditis elegans equalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin-containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression by a factor of 2. Condensin IDC and an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC's continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin IDC in X chromosome compaction, additional mechanisms contribute to X-linked gene repression. DPY-21, a non-condensin IDC DCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4, a protein that tethers H3K9me3-rich chromosomal regions to the nuclear lamina, also contributes to X-linked gene repression. To investigate the necessity of condensin IDC during the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin IDC subunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin IDC was no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression (about 1.4-fold). These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin IDC. A loss-of-function mutation in cec-4, in addition to the depletion of DPY-27 or the genetic mutation of dpy-21, led to even more significant increases in X-linked gene expression (about 1.7-fold), suggesting that CEC-4 helps stabilize repression mediated by condensin IDC and H4K20me1.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011247"},"PeriodicalIF":4.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic classification of gene-by-treatment interactions on molecular count phenotypes.","authors":"Yuriko Harigaya, Nana Matoba, Brandon D Le, Jordan M Valone, Jason L Stein, Michael I Love, William Valdar","doi":"10.1371/journal.pgen.1011561","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011561","url":null,"abstract":"<p><p>Genetic variation can modulate response to treatment (G×T) or environmental stimuli (G×E), both of which can be highly consequential in biomedicine. An effective approach to identifying G×T signals and gaining insight into molecular mechanisms is mapping quantitative trait loci (QTL) of molecular count phenotypes, such as gene expression and chromatin accessibility, under multiple treatment conditions, which is termed response molecular QTL mapping. Although standard approaches evaluate the interaction between genetics and treatment conditions, they do not distinguish between meaningful interpretations such as whether a genetic effect is observed only in the treated condition or whether a genetic effect is observed always but accentuated in the treated condition. To address this gap, we have developed a downstream method for classifying response molecular QTLs into subclasses with meaningful genetic interpretations. Our method uses Bayesian model selection and assigns posterior probabilities to different types of G×T interactions for a given feature-SNP pair. We compare linear and nonlinear regression of log ⁡ -scale counts, noting that the latter accounts for an expected biological relationship between the genotype and the molecular count phenotype. Through simulation and application to existing datasets of molecular response QTLs, we show that our method provides an intuitive and well-powered framework to report and interpret G×T interactions. We provide a software package, ClassifyGxT [1].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011561"},"PeriodicalIF":4.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}