Human Genomics最新文献

{"title":"Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort.","authors":"Qin-Meng Shu, Yu-Qiao Ju, Yuan Zong, Ting Zhang, Xin Huang, Feng-Juan Gao, Qing Chang","doi":"10.1186/s40246-025-00749-2","DOIUrl":"https://doi.org/10.1186/s40246-025-00749-2","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the reliability of clinical impressions based on ocular manifestations in patients suspected of heritable connective tissue disorders (HCTDs) compared to the final genetic diagnosis. Furthermore, it sought to determine the optimal diagnostic strategy for patients with HCTDs through pathogenicity analysis.</p><p><strong>Methods: </strong>Clinical characteristics of 58 patients suspected of HCTDs were analyzed to establish provisional clinical diagnoses. Subsequently, next-generation sequence and Sanger sequence was performed to obtain genetic diagnoses. Pathogenicity of identified variants was assessed through conservation analysis and the functional impact, which was predicted using three-dimensional protein structure modeling.</p><p><strong>Results: </strong>The provisional clinical diagnosis was concordant with the molecular diagnostic result in only 21 patients. Independent of the initial clinical impression, a probable genetic diagnosis was achieved for all 58 patients following comprehensive re-analysis of next-generation sequence data, combined with pathogenicity assessment using three-dimensional protein structure and conservation analysis of suspicious positive variants.</p><p><strong>Conclusion: </strong>This study broadens the mutational spectrum of HCTDs with 31 novel variants. By employing innovative methodologies to delineate phenotype-genotype relationships, including the detection of potentially pathogenic variants, this work may inform future diagnostic strategies and guide comprehensive disease and organ system monitoring. Ongoing refinement and vigilant clinical oversight remain essential for patients and their families.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"38"},"PeriodicalIF":3.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of trio whole exome sequencing in fetuses with ultrasound anomalies.","authors":"Ziye Zeng, Lan Zhang, Yuqin Zhou, Xue Zhang, Hong Yi, He Li, Yuqi Liu, Jian Li, Qian Chen, Yulin Chen, Guiming Yu, Jing Yi, Yana Zhang, Hua Zhang, Yanling Dong","doi":"10.1186/s40246-025-00745-6","DOIUrl":"10.1186/s40246-025-00745-6","url":null,"abstract":"<p><strong>Introduction: </strong>Ultrasound scanning anomalies in fetuses are a cause for concern and often necessitate further diagnostic procedures. This retrospective study evaluated the utility of trio whole exome sequencing (trio-WES) in the diagnosis of fetuses with ultrasound anomalies.</p><p><strong>Methods: </strong>We included fetuses diagnosed with fetal ultrasound anomalies referred to the First Affiliated Hospital of Chongqing Medical University between November 2018 and July 2023. Fetal anomalies were classified into structural anomalies, dynamic anomalies, and soft markers. Karyotype analysis, chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq) and trio-WES were performed for the eligible cases. Perinatal outcomes were recorded and evaluated at postnatal follow-up.</p><p><strong>Results: </strong>A total of 316 fetuses were included for the analysis, including 199 (63.0%) cases with structural abnormalities, 63 (19.9%) cases with dynamic abnormalities, and 54 (17.1%) fetuses with ultrasonic soft markers. The diagnostic yield of karyotyping and CMA/CNV-seq was 4.1% (13/316), and Trio-WES achieved an additional diagnosis rate of 15.8% (50/316). Pathogenic or likely pathogenic alleles (P/LP) variants of 132 genes were identified in 125 (39.6%, 125/316) cases, and variant of uncertain significance (VUS) was detected in 81 samples (25.6%, 81/316). Ten cases (3.2%, 10/316,) were found to have pathogenic karyotype or CNVs in supplementary analysis of WES. Fetuses presenting musculoskeletal anomalies and multiple anomalies demonstrated highest diagnostic rates at 36.4% (8/22) and 36.1% (13/36), respectively. The diagnostic rate of fetuses with short femur was 20% (8/40), significantly higher than other ultrasonic soft markers. The modes of inheritance observed in patients with molecular diagnoses were autosomal dominant (AD) in 66.0% cases (33/50), autosomal recessive (AR) in 26.0% cases (13/50), and X-linked (XL) in 8.0% cases (4/50).</p><p><strong>Conclusion: </strong>The integration of CMA/CNV-seq with trio-WES, alongside prenatal ultrasound scanning, holds the promise of significantly enriching our ability to decipher fetal phenotypes. This tripartite approach stands to revolutionize the diagnostic process, offering a more comprehensive and nuanced understanding of the underlying genetic architecture that underpins prenatal anomalies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"37"},"PeriodicalIF":3.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences of participants with undiagnosed diseases and hereditary cancers during the initial phase of the Hong Kong genome project: a mixed-methods study.","authors":"Annie Tw Chu, Samuel Yc Sze, Desiree Ms Tse, Cheryl Wy Lai, Carmen S Ng, Coco Ws Yu, Pui-Hong Chung, Fei-Chau Pang, Brian Hy Chung, Su-Vui Lo, Jianchao Quan","doi":"10.1186/s40246-025-00746-5","DOIUrl":"10.1186/s40246-025-00746-5","url":null,"abstract":"<p><strong>Background: </strong>The Hong Kong Genome Project (HKGP) is the first population-wide whole genome sequencing (WGS) programme in Hong Kong and aimed to integrate genomic medicine into the healthcare system. Implementing genetic counselling is essential to help participants understand the genetic basis of diseases and guide informed decision making. We assessed participant experiences during the initial HKGP pilot phase that enrolled patients with undiagnosed diseases and hereditary cancers.</p><p><strong>Methods: </strong>Participants were recruited from three partnering centres at public hospitals during June-September 2023. Participant surveys covered four domains: (1) overall satisfaction, (2) informed consent process, (3) genetic counselling, and (4) attitude towards HKGP. Associations with demographic and socioeconomic characteristics were assessed with multivariable logistic regression. Qualitative feedback was collected in focus group interviews.</p><p><strong>Results: </strong>Among 422 eligible participants, 341 completed the survey (80.8% response) and five focus group interviews were held (21 participants). We found 89.8% [95% CI: 86.1-92.7] were satisfied with their HKGP experience. Almost all felt that HKGP participation could benefit others (86.8% [95% CI: 82.7-90.0]) and advance genomic research in Hong Kong (88.9% [95% CI: 85.0-91.9]). The survey item with the lowest agreement among respondents was feeling that HKGP participation could improve their/child's medical treatment (73.5% [95% CI: 68.5-78.0]). Those with secondary and tertiary education were less likely to agree genetic counselling was helpful (Odds Ratio [OR]: 0.02 [95% CI: 0.001-0.41]; 0.02 [0.001-0.51]), or the appropriate length of time (OR: 0.12 [95% CI: 0.014-0.81]; 0.11 [0.01-0.91]). Focus group participants cited helping scientific advances and shortening the diagnostic odyssey of future patients as key reasons for participation. Participants hoped for a shorter reporting time of WGS results, additional medical follow-up, and allowing referral of relatives.</p><p><strong>Conclusions: </strong>Participants were overall highly satisfied with the HKGP and genetic counselling experience. Satisfaction levels were comparable to overseas genomic programmes and locally provided healthcare services. Participants' major concerns on WGS reporting time could be addressed by strengthening the informed consent process to ensure their expectations align with project implementation. Emphasizing the long-term value of genomic research and its potential for personalized treatments may increase participant engagement.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"36"},"PeriodicalIF":3.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of the expression patterns and diagnostic capability of the ncRNAs NEAT1 and miR-34a in non-obstructive azoospermia and severe oligospermia.","authors":"Aya Salman, Abdullah F Radwan, Olfat G Shaker, Adel A, Ghadir A Sayed","doi":"10.1186/s40246-025-00742-9","DOIUrl":"10.1186/s40246-025-00742-9","url":null,"abstract":"<p><p>Infertility is a major global health problem, affecting 8-12% of couples worldwide, with male causes contributing to approximately 50% of cases. Notably, around 15% of infertile men are azoospermic. Consequently, there is a critical necessity to find noninvasive biomarkers to help in diagnosing and assessing the susceptibility of patients with various infertility disorders. This study is designed to determine the roles of NEAT1 and miR-34a as diagnostic and susceptibility biomarkers for non-obstructive azoospermia and severe oligospermia. The interactions between these non-coding RNA (ncRNAs) were explored, along with their correlations to hormonal profiles and clinical parameters like sperm count and motility. The potential of serum NEAT1 and miR-34a as diagnostic biomarkers for these conditions was explored. The study included 100 participants: 40 non-obstructive azoospermia patients, 40 severe oligospermia patients, and 20 healthy controls. Quantitative real-time PCR and transcriptomics-based bioinformatics tools were employed to explore the co-expression networks and molecular interactions of NEAT1, miR-34a, SIRT1, and their associated hormonal and genetic pathways. Results indicated that NEAT1 was significantly downregulated in severe oligospermia patients, while its levels in non-obstructive azoospermia patients did not differ significantly from healthy controls. Furthermore, serum miR-34a expression was considerably upregulated in both patient groups compared to controls. This study highlights the promise of serum NEAT1 and miR-34a as diagnostic markers for non-obstructive azoospermia and severe oligospermia. These findings provide valuable insights into male infertility and indicate potential avenues for personalized treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"35"},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tapping natures rhythm: the role of season in mitochondrial function and genetics in the UK biobank.","authors":"Anastasios Papadam, Mihail Mihov, Adriana Koller, Hansi Weissensteiner, Klaus Stark, Felix Grassmann","doi":"10.1186/s40246-025-00743-8","DOIUrl":"10.1186/s40246-025-00743-8","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria are small organelles inside our cells crucial for producing energy and heat, cell signaling, production and degradation of important molecules, as well as cell death. The number of mitochondria in each cell is a marker for mitochondrial function, which generally declines with increasing age. However, we found that there is also a considerable seasonal variation of mitochondrial abundance, which warrants further research.</p><p><strong>Methods: </strong>We leveraged data from individuals participating in the UK Biobank study and computed their mitochondrial abundance from Exome sequencing reads mapping to the mitochondrial genome. The seasonal effect was modelled as a sine-cosine function across the year and changes in amplitude, acrophase and displacement of mitochondrial abundance due to various demographic, lifestyle, genetic, proteomic, and metabolomic markers were investigated with multivariate regression.</p><p><strong>Results: </strong>We found that mitochondrial DNA (mtDNA) abundance was higher in winter than in summer. This difference is related to advanced age, a higher BMI and smoking behavior which resulted in a reduced amplitude of mtDNA abundance. A higher education reduced the acrophase (i.e., shifted the distribution to earlier in the year) and a higher BMI and lack of physical activity led to a later acrophase. Generally, increased immune cell count resulted in lower amplitude, and an increased platelet and lymphocyte count was found to increase the acrophase. Importantly, a reduced seasonal amplitude was associated with increased risk for cardiovascular, digestive, genitourinary, and respiratory diseases as well as all-cause mortality. Most of the metabolomic and proteomic markers were associated with mtDNA displacement (i.e., increase of the baseline level) but not acrophase or amplitude. Similarly, we found that there are multiple genetic variants influencing displacement, but none reached genome-wide significance when investigating acrophase or amplitude.</p><p><strong>Conclusion: </strong>Seasonal variation of mtDNA abundance is influenced by environmental, lifestyle and immune parameters. Differences in the seasonal oscillation of mitochondrial abundance could potentially explain discrepancies of previous associations results and might be useful to improve future risk prediction.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"34"},"PeriodicalIF":3.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Displacement of distant regulatory elements of FOXC1 as a potential human disease mechanism.","authors":"Jesús-José Ferre-Fernández, Linda M Reis, Elena V Semina","doi":"10.1186/s40246-025-00735-8","DOIUrl":"10.1186/s40246-025-00735-8","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"33"},"PeriodicalIF":3.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics and clinical implications of SPINK1 in the pancreatitis continuum and pancreatic cancer.","authors":"Qi-Wen Wang, Wen-Bin Zou, Emmanuelle Masson, Claude Férec, Zhuan Liao, Jian-Min Chen","doi":"10.1186/s40246-025-00740-x","DOIUrl":"10.1186/s40246-025-00740-x","url":null,"abstract":"<p><p>Serine peptidase inhibitor, Kazal type 1 (SPINK1), a 56-amino-acid protein in its mature form, was among the first pancreatic enzymes to be extensively characterized biochemically and functionally. Synthesized primarily in pancreatic acinar cells and traditionally known as pancreatic secretory trypsin inhibitor, SPINK1 protects the pancreas by inhibiting prematurely activated trypsin. Since 2000, interest in SPINK1 has resurged following the discovery of genetic variants linked to chronic pancreatitis (CP). This review provides a historical overview of SPINK1's discovery, function, and gene structure before examining key genetic findings. We highlight three variants with well-characterized pathogenic mechanisms: c.-4141G > T, a causative enhancer variant linked to the extensively studied p.Asn34Ser (c.101A > G), which disrupts a PTF1L-binding site within an evolutionarily conserved HNF1A-PTF1L cis-regulatory module; c.194 + 2T > C, a canonical 5' splice site GT > GC variant that retains 10% of wild-type transcript production; and an Alu insertion in the 3'-untranslated region, which causes complete loss of function by forming extended double-stranded RNA structures with pre-existing Alu elements in deep intronic regions. We emphasize the integration of a full-length gene splicing assay (FLGSA) with SpliceAI's predictive capabilities, establishing SPINK1 the first disease gene for which the splicing impact of all possible coding variants was prospectively determined. Findings from both mouse models and genetic association studies support the sentinel acute pancreatitis event (SAPE) model, which explains the progression from acute pancreatitis to CP. Additionally, SPINK1 variants may contribute to an increased risk of pancreatic ductal adenocarcinoma (PDAC). Finally, we discuss the therapeutic potential of SPINK1, particularly through adeno-associated virus type 8 (AAV8)-mediated overexpression of SPINK1 as a strategy for treating and preventing pancreatitis, and highlight key areas for future research.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"32"},"PeriodicalIF":3.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic risk factors associated with ocular perfusion pressure in primary open-angle glaucoma.","authors":"Heejin Jin, Je Hyun Seo, Young Lee, Sungho Won","doi":"10.1186/s40246-025-00738-5","DOIUrl":"10.1186/s40246-025-00738-5","url":null,"abstract":"<p><strong>Background: </strong>Primary open-angle glaucoma (POAG) is the leading cause of irreversible vision loss. However, its genetic risk factors, such as the vascular hypothesis of POAG, remain unclear. Here, we aimed to explore the genetic associations between mean ocular perfusion pressure (MOPP) and POAG. We performed genome-wide analysis with gene-based analysis from the UK Biobank (N = 459,195), which includes genetic data and ocular phenotypes. Bidirectional two-sample Mendelian randomisation (MR), multivariable MR, and mediation analysis were conducted using summary statistics from a previous meta-analysis of genome-wide association studies (N = 216,257).</p><p><strong>Results: </strong>CEP85L, GRIA4, GRIN2A, LRFN5, MAGI1, POU6F2, RBFOX1, RBMS1, RBMS3, RBPMS, TRHDE, TUBB3, ZFHX3, and ZMAT4 were significantly correlated with various ocular phenotypes. Furthermore, POAG shared strong genetic associations with corneal resistance factor (CRF), intraocular pressure (IOP), refractive error (RE), and MOPP but none with corneal hysteresis (CH). Univariable MR showed a negative causal effect of CH, CRF, and MOPP and a positive causal effect of IOP on POAG occurrence. In multivariable MR, MOPP exhibited a direct causal effect on POAG, which was supported by the mediation analysis results.</p><p><strong>Conclusions: </strong>We successfully determined 14 genetic loci related to CH, CRF, IOP, RE, and MOPP. In univariable and multivaribale MR analyses, a causal effect of MOPP on POAG were observed. In addition, the mediation analysis supported that MOPP exerted direct and indirect causal effects on POAG. This finding indicates that MOPP may serve as a potential causal factor in POAG, providing valuable insights into the pathophysiology of POAG as vascular theory.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"31"},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and validation of a DIP panel for forensic ancestry inference and personal identification.","authors":"Shuanglin Li, Shuyan Mei, Yanfang Liu, Wei Cui, Bofeng Zhu","doi":"10.1186/s40246-025-00727-8","DOIUrl":"10.1186/s40246-025-00727-8","url":null,"abstract":"<p><strong>Background: </strong>Biallelic Deletion/Insertion polymorphisms (DIPs), known for their significant diversity across various populations, serve as valuable markers for forensic ancestry inference and personal identification. In this study, we utilized DIPs to provide a potentially powerful forensic examination tool specifically tailored for East Asian populations. Our focus on ancestry allows us to delve deeper into the genetic signatures that characterize this diverse group, offering enhanced resolution in forensic analyses.</p><p><strong>Methods: </strong>A total of 56 autosomal DIPs, 3 Y-chromosome DIPs, and the Amelogenin were selected to build the 60-panel. Population genetic parameters, principal component analysis (PCA), STRUCTURE analysis, and phylogenetic tree construction were employed to evaluate the capacity for ancestry inference. The verification guidelines recommended by the Scientific Working Group on DNA Analysis Methods were followed in the developmental validations of the 60-panel.</p><p><strong>Results: </strong>The PCA, STRUCTURE, and phylogenetic tree constructions were not only consistent with each other but also corroborated by previous research. The combined probability of discrimination and the cumulative probability of paternity exclusion values were 0.999999999999 and 0.9937, respectively. These values indicate that the 60-panel is not only a useful tool for personal identification testing within the East Asian population but also provides valuable biogeographic information. Furthermore, the validation study of the 60-panel, which included assessments of PCR conditions, sensitivity, species specificity, stability, mixture analysis, reproducibility, and case sample studies, as well as analysis of degraded samples, demonstrated that the panel is well-suited for forensic testing. The panel's performance was particularly notable in the analysis of degraded samples, showcasing its potential for use in challenging forensic cases.</p><p><strong>Conclusion: </strong>The newly developed 60-panel demonstrated robust performance in validation tests, yielding reliable genotypes even from poor-quality samples like degraded DNA. It offers valuable biogeographic insights and sufficient polymorphism for personal identification, which assisted forensic examinations in East Asian populations.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"30"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying behavior regulatory leverage over mental disorders transcriptomic network hubs toward lifestyle-dependent psychiatric drugs repurposing.","authors":"Mennatullah Abdelzaher Turky, Ibrahim Youssef, Azza El Amir","doi":"10.1186/s40246-025-00733-w","DOIUrl":"10.1186/s40246-025-00733-w","url":null,"abstract":"<p><strong>Background: </strong>There is a vast prevalence of mental disorders, but patient responses to psychiatric medication fluctuate. As food choices and daily habits play a fundamental role in this fluctuation, integrating machine learning with network medicine can provide valuable insights into disease systems and the regulatory leverage of lifestyle in mental health.</p><p><strong>Methods: </strong>This study analyzed coexpression network modules of MDD and PTSD blood transcriptomic profile using modularity optimization method, the first runner-up of Disease Module Identification DREAM challenge. The top disease genes of both MDD and PTSD modules were detected using random forest model. Afterward, the regulatory signature of two predominant habitual phenotypes, diet-induced obesity and smoking, were identified. These transcription/translation regulating factors (TRFs) signals were transduced toward the two disorders' disease genes. A bipartite network of drugs that target the TRFS together with PTSD or MDD hubs was constructed.</p><p><strong>Results: </strong>The research revealed one MDD hub, the CENPJ, which is known to influence intellectual ability. This observation paves the way for additional investigations into the potential of CENPJ as a novel target for MDD therapeutic agents development. Additionally, most of the predicted PTSD hubs were associated with multiple carcinomas, of which the most notable was SHCBP1. SHCBP1 is a known risk factor for glioma, suggesting the importance of continuous monitoring of patients with PTSD to mitigate potential cancer comorbidities. The signaling network illustrated that two PTSD and three MDD biomarkers were co-regulated by habitual phenotype TRFs. 6-Prenylnaringenin and Aflibercept were identified as potential candidates for targeting the MDD and PTSD hubs: ATP6V0A1 and PIGF. However, habitual phenotype TRFs have no leverage over ATP6V0A1 and PIGF.</p><p><strong>Conclusion: </strong>Combining machine learning and network biology succeeded in revealing biomarkers for two notoriously spreading disorders, MDD and PTSD. This approach offers a non-invasive diagnostic pipeline and identifies potential drug targets that could be repurposed under further investigation. These findings contribute to our understanding of the complex interplay between mental disorders, daily habits, and psychiatric interventions, thereby facilitating more targeted and personalized treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"29"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}