Advanced genetics (Hoboken, N.J.)最新文献

{"title":"Editorial Board: (Advanced Genetics 2/06)","authors":"","doi":"10.1002/ggn2.70004","DOIUrl":"https://doi.org/10.1002/ggn2.70004","url":null,"abstract":"","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding RNA–Protein Interactions: Methodological Advances and Emerging Challenges (Advanced Genetics 2/06)","authors":"Wenkai Yi,&nbsp;Jian Yan","doi":"10.1002/ggn2.70001","DOIUrl":"https://doi.org/10.1002/ggn2.70001","url":null,"abstract":"<p><b>RNA–Protein Interactions</b></p><p>This cover art symbolizes RNA-protein interaction methodologies. The boy's fishing line represents RNA bait, while the hooked carp embodies RNA-binding proteins captured via dynamic interplay. In article number 2500011, Wenkai Yi and Jian Yan dissect cutting-edge techniques–from RNA-centric to protein-centric–that decode these molecular dialogues, emphasizing their roles in gene regulation and disease. The metaphor underscores how innovative tools “reel in” elusive targets, bridging mechanistic discovery with therapeutic potential.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Dialogues: From Genomes to Microbiomes—A Cross-Disciplinary Journey","authors":"Jingyuan Fu","doi":"10.1002/ggn2.202500039","DOIUrl":"https://doi.org/10.1002/ggn2.202500039","url":null,"abstract":"&lt;p&gt;My research group, Integrative Omics in Systems Medicine, is affiliated at the University Medical Center Groningen, the Netherlands. Our research aims to understand host-microbe interactions in complex traits and diseases, for which we integrate genetics, microbiome, and large-scale omics data to identify risk factors and their interactions underlying inter-individual variation in disease susceptibility.&lt;/p&gt;&lt;p&gt;The most pressing challenges lie in the undefined causality and molecular mechanisms underlying observed associations. In the post-GWAS and big data era, many genetic loci, microbial species, and other risk factors have been linked to various phenotypes. However, the translation of these findings into personalized medicine remains limited. I see promising opportunities in two areas. First, recent advances in artificial intelligence (AI) are facilitating genome annotation, risk prediction, and drug target discovery. Second, microfluidic organ-on-a-chip technologies, combined with the differentiation and culturing of human induced pluripotent stem cells (hiPSCs), enable the construction of individualized organ-on-a-chip systems for studying disease mechanisms and testing drugs, all while accounting for a person's unique genetic background.&lt;/p&gt;&lt;p&gt;My scientific journey has three important turning points. I received my bachelor's degree in biochemistry and switched to the field of bioinformatics for my master's. This was the first turning point that enabled me to establish my knowledge in both molecular biology and bioinformatics. The second turning point was when I successfully completed my Ph.D. project in systems genetics using a plant model organism in 2007. At the time, the first draft sequence of the human genome was just published, and genome-wide association studies (GWAS) began to emerge for genome-wide genetic screening. I saw an opportunity to extend my expertise from plant genomics to human genetics. This chance permitted me to cross the disciplinary border toward the field of medicine. The third turning point took place in 2013 when I further extended my research area from human genetics to the human gut microbiome. The first microbiome study was published in &lt;i&gt;Circulation Research&lt;/i&gt; in 2015&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;],&lt;/sup&gt; which was highlighted in the &lt;i&gt;TIME&lt;/i&gt; book “TIME 100 New Health Discoveries: How the latest breakthroughs affect your health and wellness”.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Then in 2016, our first metagenome-based study was published in &lt;i&gt;Science&lt;/i&gt;, which was also highlighted on the cover.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; These two studies marked the beginning of my scientific journey in the microbiome field. Recently, our studies revealed inter-individual differences in the gut microbiome and the underlying environmental and genetic factors&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt;, reported its temporal dynamics and stability,&lt;sup&gt;[&lt;/sup&gt;&lt;sp","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202500039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoplatform-Enabled Genetic Interventions for Central Nervous System Disorders: Advances in Delivery Strategies and Therapeutic Potential","authors":"Fuming Liang,&nbsp;Shizhen Cui,&nbsp;Jing Yang,&nbsp;Zhaohui He,&nbsp;Ling Zhu","doi":"10.1002/ggn2.202500010","DOIUrl":"https://doi.org/10.1002/ggn2.202500010","url":null,"abstract":"<p>Central nervous system (CNS) disorders are driven by complex genetic and epigenetic factors. While gene-based interventions (siRNA, mRNA, CRISPR systems, etc.) hold transformative potential, their clinical application is severely constrained by inefficient delivery, especially across the blood-brain barrier. Nanocarriers have emerged as transformative platforms that overcome these challenges by enabling efficient BBB penetration while ensuring precise biodistribution control and enhanced therapeutic payload protection. This review explores recent advances in nanoplatform-enabled genetic intervention that overcome the delivery challenges through innovative engineering approaches. We discuss the genetic and epigenetic mechanisms underlying major CNS pathologies, the current limitations of free nucleic acid therapeutics, the development of advanced nanoplatforms that achieve blood-brain barrier penetration and targeted delivery. We further also evaluate therapeutic prospects across disease models while addressing translational challenges in stability, targeting specificity, and manufacturing scalability. By integrating fundamental research with preclinical applications, this review provides both a theoretical framework and practical roadmap for developing next-generation nanotherapeutics for CNS genetic medicine.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202500010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding RNA–Protein Interactions: Methodological Advances and Emerging Challenges","authors":"Wenkai Yi,&nbsp;Jian Yan","doi":"10.1002/ggn2.202500011","DOIUrl":"https://doi.org/10.1002/ggn2.202500011","url":null,"abstract":"<p>RNA–protein interactions are fundamental to cellular processes such as gene regulation and RNA metabolism. Over the past decade, significant advancements in methodologies have transformed the ability to study these interactions with unprecedented resolution and specificity. This review systematically compares RNA- and protein-centric approaches, highlighting their strengths, limitations, and optimal applications. RNA-centric methods, including hybridization-based pulldowns, proximity labeling, and CRISPR-assisted techniques, enable the identification of proteins interacting with specific RNAs, even low-abundance or transient partners. Protein-centric strategies, such as immunoprecipitation-based CLIP-seq, and emerging proximity-tagging methods, map RNA interactomes of RNA-binding proteins with nucleotide precision. This study evaluates key innovations like LACE-seq and ARTR-seq, which minimize cell input requirements, and HyPro-MS, which bypasses genetic modifications. Guidelines for method selection are provided, emphasizing experimental goals, RNA abundance, interaction dynamics, and technical constraints. Critical challenges are also discussed, including capturing low-affinity interactions, resolving RNA structural complexities, and integrating multi-omics data. This review underscores the importance of method-tailoring to biological contexts, offering a roadmap for researchers to navigate the evolving landscape of RNA–protein interaction studies. By bridging technical advancements with practical recommendations, this study aims to accelerate discoveries in RNA biology, therapeutic development, and precision medicine.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202500011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of the Rs1044457 Polymorphism in the CMPK1 Gene on the Response Rate to Gemcitabine-Based Chemotherapy in Metastatic NSCLC Patients","authors":"Ghassan Saod Saleh,&nbsp;Fouad Kadhim Gatea,&nbsp;Qasim Sharhan Al-Mayah,&nbsp;Hayder Lazim","doi":"10.1002/ggn2.202400058","DOIUrl":"https://doi.org/10.1002/ggn2.202400058","url":null,"abstract":"<p>This study aims to evaluate the role of a specific gene polymorphism, Cytidine/Uridine Monophosphate Kinase 1 (CMPK1) rs1044457, in predicting the response to gemcitabine-based chemotherapy in patients with NSCLC. A total of 98 NSCLC patients are enrolled in the study. Based on their response, patients are classified as either responders or non-responders. Specific primers are designed to amplify the rs1044457 variant and performed genotyping using restriction fragment length polymorphism (RFLP). The rs1044457 variant showed a statistically significant difference in frequency between responder and non-responder patients. The mutant genotype (TT) is more frequent in non-responder patients (18.75%) compared to responder patients (4%), with an odds ratio [OR] of 5.93 (95% confidence interval [CI] = 1.16–30.25, p = 0.032). Additionally, at the allelic level, the mutant allele (T) is more common in non-responder patients (36.46%) compared to responder patients (23%), with a statistically significant odds ratio of 1.92 (95% CI = 1.03–3.58, p = 0.040). The findings of this study suggest that the mutant allele (allele T) of the rs1044457 variant may serve as a risk factor for resistance to gemcitabine-based chemotherapy in patients with NSCLC.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202400058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board: (Advanced Genetics 1/06)","authors":"","doi":"10.1002/ggn2.202570012","DOIUrl":"https://doi.org/10.1002/ggn2.202570012","url":null,"abstract":"","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202570012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(Advanced Genetics 1/06)","authors":"","doi":"10.1002/ggn2.202570011","DOIUrl":"https://doi.org/10.1002/ggn2.202570011","url":null,"abstract":"","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202570011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-Wide Mendelian Randomization Identifies Candidate Causal Proteins for Cardiovascular Diseases","authors":"Chen Li,&nbsp;Nicolas De Jay,&nbsp;Shan-Shan Zhang,&nbsp;Xin Fang,&nbsp;Supriya Sharma,&nbsp;Katrina A. Catalano,&nbsp;Venkatesh Sridharan,&nbsp;Zhaoqing Wang,&nbsp;Lei Zhao,&nbsp;Joseph D. Szustakowski,&nbsp;Ching-Pin Chang,&nbsp;Joseph C. Maranville,&nbsp;Emily R. Holzinger,&nbsp;Erika M. Kvikstad","doi":"10.1002/ggn2.202500003","DOIUrl":"https://doi.org/10.1002/ggn2.202500003","url":null,"abstract":"<p>Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR &lt; 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202500003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Cohort Analysis Reveals Genetic Predispositions to Clonal Hematopoiesis as Mutation-Specific Risk Factors for Stroke","authors":"Shuyang Lin,&nbsp;Yang E. Li,&nbsp;Yan Wang","doi":"10.1002/ggn2.202400047","DOIUrl":"https://doi.org/10.1002/ggn2.202400047","url":null,"abstract":"<p>Recent observational studies have found an association between Clonal Hematopoesis (CH) and strokes but with incomplete results. This study aims to comprehensively characterize mutation-specific effects of CH on ischemic and hemorrhagic stroke subtypes and 90-day functional outcomes through publicly available genome-wide association study (GWAS) cohorts and Mendelian Randomization. TET2 is associated with an increased risk of overall stroke (OR = 1.06, <i>P</i> = 0.02), ischemic stroke (OR = 1.05, <i>P</i> = 0.03), transient ischemic attack (OR = 1.07, <i>P</i> = 0.01) and small vessel stroke (OR = 1.29, <i>P</i> = 0.01), as well as adverse 90-day modified Rankin scale (mRS ≥ 3) before (OR = 1.34, <i>P</i> = 0.005) and after adjusted for age, sex, and stroke severity (OR = 1.30, <i>P</i> = 0.02). While the presence of any CH mutation is associated with intracerebral hemorrhage (ICH) (OR = 1.21, <i>P</i> = 0.02), specific mutations, SRSF2 and ASXL1 are protective against ICH (OR = 0.9, <i>P</i> = 0.04) and nontraumatic subarachnoid hemorrhage (OR = 0.92, <i>P</i> = 0.03), respectively. In conclusion, the study provided genetic evidence that TET2 is strongly associated with an increased risk of ischemic stroke and poor functional recovery. Future studies clarifying the relationship between CH and hemorrhagic stroke subtypes are needed.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202400047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}