Frontiers in Genetics最新文献

{"title":"Clinical impact of pharmacogenomics in pediatric care: insights extracted from clinical exome sequencing.","authors":"Simran Maggo, Yachen Pan, Dejerianne Ostrow, Jenny Q Nguyen, Jaclyn A Biegel, Matthew A Deardorff, Xiaowu Gai","doi":"10.3389/fgene.2025.1574325","DOIUrl":"10.3389/fgene.2025.1574325","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacogenomic (PGx) testing improves drug efficacy and reduces risk of toxicity for commonly prescribed medications, with most pharmacogenomic studies largely focused on individuals of European descent to date. The impact of pharmacogenomic testing in a racially diverse population is still emerging, especially for Admixed American patients.</p><p><strong>Methods: </strong>In this study, we assessed the frequency of actionable PGx variants by analyzing anonymized exome sequencing data of a racially diverse cohort of 1777 pediatric patients, collected for routine clinical genetic diagnosis at Children's Hospital Los Angeles (CHLA). Utilizing exome data, we used the Illumina DRAGEN germline pipeline v4.2, to determine the predicted phenotypes of 25 pharmacogenes including <i>HLA-A</i> and <i>HLA-B</i>, including CPIC Level A genes and genes recommended for PGx testing by the U.S. Food and Drug Administration. To assess cross-platform consistency, we compared our results to those generated by PyPGx, a pharmacogenomic genotyping tool developed by the same author as Stargazer. As the distribution of PGx alleles is ancestry specific, we estimated genetic ancestry bioinformatically using the Somalier tool.</p><p><strong>Results: </strong>Genetic ancestry analysis demonstrated that 62% of our cohort was Admixed American, followed by 23% European, 8% East Asian, 5% African American, and 2% South East Asian. Actionability analysis showed that: 1) 93% of all exome cases had at least one actionable PGx phenotype, 2) one in five cases (22%) had at least three actionable PGx phenotypes, and 3) CYP2B6 (54%) and CYP2D6 (33%) had the highest number of actionable phenotypes. Further analysis revealed notable differences, including higher rates of poor metabolizers for CYP2B6 and variations in CYP2D6 metabolizer statuses, in PGx phenotypes compared to previously collated frequencies in the PharmGKB database, especially within the Admixed American population.</p><p><strong>Discussion: </strong>In conclusion, our study reinforces the importance of PGx testing, underscores the diversity of PGx variation in ancestral backgrounds, and supports the clinical utility of preemptive PGx testing using exome or genome sequencing approaches.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1574325"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Computational genomic and precision medicine.","authors":"Zeeshan Ahmed, Ramkumar Thirunavukarasu, Atlas Khan","doi":"10.3389/fgene.2025.1631668","DOIUrl":"10.3389/fgene.2025.1631668","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1631668"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Statistical approaches, applications, and software for longitudinal microbiome data analysis and microbiome multi-omics data integration.","authors":"Huilin Li, Jun Chen, Mogens Fenger, Yuan Jiang","doi":"10.3389/fgene.2025.1624791","DOIUrl":"10.3389/fgene.2025.1624791","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1624791"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the role of pyrabactin-like receptors of finger millet under drought and salinity stress: an insight into <i>in silico</i>, machine learning and molecular approaches.","authors":"Varsha Rani, Theivanayagam Maharajan, Shefali Singh, D C Joshi, Ramwant Gupta, Dinesh Yadav","doi":"10.3389/fgene.2025.1598523","DOIUrl":"10.3389/fgene.2025.1598523","url":null,"abstract":"<p><strong>Introduction: </strong>The Pyrabactin Resistance 1-like (PYL) receptors, a family of proteins in plants, play a vital role in abscisic acid (ABA) signalling, assisting plants in managing abiotic stresses. Finger millet (<i>Eleusine coracana</i> (L.) Gaertn) is a naturally drought tolerant crop, yet the receptor proteins involved in its stress signalling pathways remain poorly understood.</p><p><strong>Method: </strong>This study employed bioinformatics, machine learning, and molecular approaches to identify, characterize, and profile the expression of PYL receptors in response to drought and salinity stress.</p><p><strong>Results: </strong>The study identified 14 <i>PYL</i> genes in the finger millet genome, irregularly distributed across four of the nine mapped chromosomes. Phylogenetic analysis grouped these genes into three subfamilies. Machine learning analysis highlighted five putative PYL genes-<i>EcPYL4-2A, EcPYL7-2B, EcPYL11-5A, EcPYL12-5A</i>, and <i>EcPYL14-5B</i> with expression levels exceeding 70% under drought and salinity stress. These genes were further validated through qRT-PCR, confirming their expression under stress conditions, though expression levels varied across tissues and genes.</p><p><strong>Discussion: </strong>The identification of PYL genes responsive to drought and salt stress provides valuable insights into the stress-signalling mechanisms of finger millet. Among the identified genes, <i>EcPYL7-2B</i> and <i>EcPYL12-5A</i> emerged as promising candidates for further characterization through genome editing and molecular approaches. This study highlights the potential of these genes in enhancing the stress resilience of finger millet, contributing to its role in improving food and nutritional security under challenging environmental conditions.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598523"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: High-throughput sequencing-based investigation of chronic disease markers and mechanisms, volume II.","authors":"Hua Li, Guoshuai Cai, Wen-Lian Chen, Xiaodong Zhao, Yuriy L Orlov","doi":"10.3389/fgene.2025.1627976","DOIUrl":"10.3389/fgene.2025.1627976","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1627976"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MultiV_Nm: a prediction method for 2'-O-methylation sites based on multi-view features.","authors":"Lei Bai, Fei Liu, Yile Wang, Junle Su, Lian Liu","doi":"10.3389/fgene.2025.1608490","DOIUrl":"10.3389/fgene.2025.1608490","url":null,"abstract":"<p><p>As a crucial class of chemical modifications, 2'-O-methylation modification (abbreviated as Nm) is widely distributed in various organisms and plays a very important role in normal cellular physiological activities and the occurrence and development of diseases. Accurate prediction of Nm modification sites can provide important references for the diagnosis and treatment of diseases, as well as identifying for potential drug targets. Aiming at the current problems of unstable performance caused by the use of single features and the need to improve the prediction accuracy of Nm modification sites, this paper proposes MultiV_Nm, a prediction method for Nm sites based on multi-view features. MultiV_Nm extracts the features of Nm sites from multiple dimensions, including sequence features, chemical characteristics, and secondary structure features. By integrating the powerful local feature extraction ability of convolutional neural networks, the ability of graph attention networks to capture global structural information, and the efficient interaction advantage of cross-attention mechanisms for different features, it deeply explores and integrates multi-view features, and finally realizes the prediction of Nm modification sites. The results of cross-validation and independent tests show that this method exhibits significant advantages in key evaluation indicators such as precision, recall, and accuracy, and can effectively improve Nm sites prediction performance. The proposal of MultiV_Nm not only provides a powerful tool for the study of Nm modification but also offers new ideas for predicting other RNA modification sites.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1608490"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering codon usage patterns during murine embryogenesis and tissue-specific developmental diseases.","authors":"Sarah E Fumagalli, Sean Smith, Brian Lin, Rahul Paul, Collin Campbell, Luis Santana-Quintero, Anton Golikov, Juan Ibla, Haim Bar, Anton A Komar, Ryan C Hunt, Michael DiCuccio, Chava Kimchi-Sarfaty","doi":"10.3389/fgene.2025.1554773","DOIUrl":"10.3389/fgene.2025.1554773","url":null,"abstract":"<p><strong>Introduction: </strong>Mouse models share significant genetic similarities with humans and have expanded our understanding of how embryonic tissue-specific genes influence disease states. By improved analyses of temporal, transcriptional data from these models, we can capture unique tissue codon usage patterns and determine how deviations from these patterns can influence developmental disorders.</p><p><strong>Methods: </strong>We analyzed transcriptomic-weighted data from four mouse strains across three different germ layer tissues (liver, heart, and eye) and through embryonic stages. Applying a multifaceted approach, we calculated relative synonymous codon usage, reduced the dimensionality, and employed machine learning clustering techniques.</p><p><strong>Results and discussion: </strong>These techniques identified relative synonymous codon usage differences/similarities among strains and deviations in codon usage patterns between healthy and disease-linked genes. Original transcriptomic mouse data and RefSeq gene sequences can be found at the associated Mouse Embryo CoCoPUTs (codon and codon pair usage tables) website. Future studies can leverage this resource to uncover further insights into the dynamics of embryonic development and the corresponding codon usage biases that are paramount to understanding disease processes of embryologic origin.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1554773"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic association of ACE2 rs2285666 (C>T) and rs2106809 (A>G) and susceptibility to SARS-CoV-2 infection among the Ghanaian population.","authors":"Alexander Owusu Boakye, Christian Obirikorang, Anthony Afum-Adjei Awuah, Evans Asamoah Adu, Doris Winter, Eric Ebenezer Boham, Hakim Alani, Sylvester Kofi Newton, Nana Safi Toure Almoustapha, James Deke, Welbeck Odame Dzadey, Louis Adu-Amoah, Sally-Ann Kroduah, Mary Ama Grant, Gracelyn Asare, Amos Amoako-Adusei, Wibke Loag, Jenny Kettenbeil, Yaw Adu Sarkodie, Ebenezer Oduro-Mensah, Alfred Edwin Yawson, Stephen Apanga, Rose Odotei Adjei, Austin Gideon Adobasom-Anane, Eva Lorenz, Aurélia Souares, Oumou Maiga-Ascofaré, Jürgen May, Nicole S Struck, John Humphery Amuasi","doi":"10.3389/fgene.2025.1555515","DOIUrl":"10.3389/fgene.2025.1555515","url":null,"abstract":"<p><strong>Background: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters human cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. ACE2 single nucleotide polymorphisms (SNPs) can influence susceptibility by affecting viral binding or gene expression. This study investigated the association between ACE2 SNPs, rs2285666 and rs2106809, and the SARS-CoV-2 infection susceptibility in a Ghanaian population.</p><p><strong>Methods: </strong>Genomic DNA was extracted, using a magnetic bead-based method, from blood samples of a random-subset of 1,334 participants drawn from a two-stage cluster, population-based household cross-sectional SARS-CoV-2 IgG seroprevalence survey. Data collected included, socio-demographic characteristics, medical history, vaccination, and smoking status. Genotyping of the ACE2 SNPs was performed using Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) combined with melting curve analysis. Logistic regression models were utilized to assess the association between the ACE2 SNPs and the susceptibility to SARS-CoV-2 infection.</p><p><strong>Results: </strong>The median age of participants was 33 [Interquartile range (IQR) = 24-46] years. Females accounted for the majority of the sampled population, 64.3%. SARS-CoV-2-IgG seropositivity was (58.4%, 95%CI: 52.6%-64.2%) among the male population and (54.1%, 95%CI: 49.54%-58.61%) in the female population. There were no significant differences in overall allele or genotype frequencies of ACE2 SNPs between SARS-CoV-2 IgG seropositive and seronegative individuals for both females and males. Among females, those with the T allele of ACE2 rs2285666 had a 38% decreased susceptibility to SARS-CoV-2 infection under the dominant [adjusted odds ratio (aOR) = 0.62; 95%CI = 0.45-0.85, P = 0.003] and heterozygous advantage models (aOR = 0.62; 95%CI = 0.45-0.86, P = 0.004), after adjusting for confounders, but not thee recessive model (aOR = 0.41; 95%CI = 0.03-5.22, P = 0.490). No significant association was observed among males. Overall, the ACE2 rs2106809 was not associated with the susceptibility to SARS-CoV-2 infection in both males and females.</p><p><strong>Conclusion: </strong>This study found no association between ACE2 rs2106809 genetic variant and susceptibility to SARS-CoV-2 infection, whilst the rs2285666 T-allele was associated with a decreased frequency for SARS-CoV-2 infection among Ghanaian females. These findings enhance our understanding of genetic factors influencing SARS-CoV-2 susceptibility, which could help identify at-risk populations and inform more targeted public health interventions in future outbreaks.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1555515"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of mild cognitive impairment using blood multi-omics data.","authors":"Daniel Frank Zhang, Cigdem Sevim Bayrak, Qi Zeng, Minghui Wang, Bin Zhang","doi":"10.3389/fgene.2025.1552063","DOIUrl":"10.3389/fgene.2025.1552063","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) represents an initial phase of memory or other cognitive function decline and is viewed as an intermediary stage between normal aging and Alzheimer's disease (AD), the most prevalent type of dementia. Individuals with MCI face a heightened risk of progressing to AD, and early detection of MCI can facilitate the prevention of such progression through timely interventions. Nonetheless, diagnosing MCI is challenging because its symptoms can be subtle and are easily missed. Using genomic data from blood samples has been proposed as a non-invasive and cost-efficient approach to build machine learning predictive models for assisting MCI diagnosis. However, these models often exhibit poor performance. In this study, we developed an XGBoost-based machine learning model with AUC (the Area Under the receiver operating characteristic Curve) of 0.9398 utilizing gene expression and copy number variation (CNV) data from patient blood samples. We demonstrated, for the first time, that data at a genome structure level such as CNVs could be as informative as gene expression data to classify MCI patients from normal controls. We identified 149 genomic features that are important for MCI prediction. Notably, these features are enriched in the pathways associated with neurodegenerative diseases, such as neuron development and G protein-coupled receptor activity. Overall, our study not only demonstrates the effectiveness of utilizing blood sample-based multi-omics for predicting MCI, but also provides insights into crucial molecular characteristics of MCI.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1552063"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A neurodevelopmental disorder with global developmental delay, microcephaly, eye anomalies, sweat dysregulation, and skeletal implications due to an ultra-rare <i>de novo</i> 5q14.3q15 copy number gain.","authors":"Costela Lacrimioara Serban, Alexandra Mihailescu, Diana Miclea, Cristian G Zimbru, Florina Stoica, Adela Chirita-Emandi","doi":"10.3389/fgene.2025.1549685","DOIUrl":"10.3389/fgene.2025.1549685","url":null,"abstract":"<p><p>This case report and literature review documents an ultra-rare <i>de novo</i> copy number gain at 5q14.3q15. The patient's phenotype included hypotonia, microcephaly, global developmental delay, iris hypoplasia, atrophy, sweat dysregulation, and skeletal implications, including camptodactyly. This case presentation provides novel insights into the genotype-phenotype correlation for 5q14.3q15 copy number gain, particularly highlighting the involvement of the <i>MEF2C</i> gene (#MIM 600662). Through comprehensive clinical and genetic evaluation, we aim to enhance the understanding of this ultra-rare genetic condition and its implications.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1549685"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}