Human Genomics最新文献

{"title":"Carrier rates for recessive monogenic diseases in the Chinese Han population: a systematic review.","authors":"Yirong Xia, Yinan Ma","doi":"10.1186/s40246-026-00940-z","DOIUrl":"10.1186/s40246-026-00940-z","url":null,"abstract":"<p><p>OBJECTIVE: In China, research on expanded carrier screening (ECS) has exhibited significant inconsistencies due to regional variations, with a lack of large-scale data analysis of the population nationwide. This study aimed to review the carrier rates of monogenic disorders throughout China comprehensively. METHODS: The study was conducted in two stages, with the carrier rate of monogenic diseases as the primary outcome. In the first stage, 1449 articles were identified, of which 11 were ultimately included for data extraction. In the second stage, all 307 genes identified by the first stage were specifically investigated, and both carrier rates and allele frequencies of pathogenic or likely pathogenic (P/LP) variants were extracted. RESULTS: Nineteen genes were associated with monogenic disorders exhibiting carrier frequencies above 1/100, including GJB2 (7.78%), HBA1/2 (6.19%), PAH (2.76%), ATP7B (2.51%), DUOX2 (2.50%), HBB (2.48%), GALC (2.37%), CYP21A2 (2.11%), SLC26A4 (1.96%), POLG (1.92%), USH2A (1.91%), SLC25A13 (1.87%), SLC22A5 (1.78%), SMN1 (1.75%), MMACHC (1.66%), G6PD (1.38%), GAA (1.05%), UGT1A1 (1.02%), and TYR (1.01%). Twenty-seven conditions had carrier rates between 1/100 and 1/200, and thirty had carrier frequencies between 1/200 and 1/400. The ten most common pathogenic/likely pathogenic (P/LP) variants with the highest allele frequencies were: GJB2 c.109G>A (7.3%), POLG c.2890C>T (0.94%), GALC c.1901T>C (0.90%), SMN1 exon 7 deletion (0.87%), SLC25A13 c.2T>C (0.59%), SLC22A5 c.1472C>G (0.52%), GJB2 c.235del (0.50%), SLC22A5 c.1400C>G (0.48%), SLC22A5 c.43G>T (0.44%), and SLC25A13 c.852_855del (0.43%). CONCLUSION: This review provides the first comprehensive summary of carrier rates for monogenic diseases in the Chinese Han population. It not only describes but also ranks the carrier rates and variant frequencies of related genes, offering critical evidence for the tiered inclusion of gene categories in ECS panels or newborn screening programs.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343910","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":"Unravelling genetic susceptibility and causal factors in liver health using MRI quantification of inflammation, fat and iron in the liver.","authors":"Devendra Meena, Michele Pansini, Alessandro Fichera, Jingxian Huang, Altayeb Ahmed, Abbas Dehghan, Rajarshi Banerjee, Hanieh Yaghootkar","doi":"10.1186/s40246-026-00913-2","DOIUrl":"10.1186/s40246-026-00913-2","url":null,"abstract":"<p><p>BACKGROUND: Liver steatosis, fibroinflammation, and iron overload, are growing global health concerns, yet the genetic architecture and causal pathways linking liver pathology to systemic disease remain incompletely understood. METHODS: We analysed MRI-derived liver traits—corrected T1 (cT1), proton density fat fraction (PDFF), and liver iron—in 37,626 UK Biobank participants. Genome-wide (GWAS), transcriptome-wide (TWAS), and cis-protein Mendelian randomisation (cis-MR) analyses were used to identify genes and proteins influencing these traits. We applied two-sample MR to assess bidirectional causal relationships with metabolic and vascular traits and used Multi-Trait Analysis of GWAS (MTAG) to enhance discovery by leveraging genetic correlations. RESULTS: GWAS identified 18 loci for cT1, 15 for PDFF, and 5 for liver iron, including six not previously reported. TWAS, cis-MR, and proteome-wide analyses prioritised genes (e.g., FADS1, GPAM, MBOAT7, RAD51C) and proteins (e.g., RAB2B, GPN1, GSTM4) with putative mechanistic roles. Fine-mapping refined several signals (GSTM1, TMPRSS6) to single-variant credible sets. Cell-type enrichment revealed distinct tissue contributions: hepatocytes and intestinal mucosa for cT1, adipose tissue for PDFF, and gastrointestinal tissues for liver iron. MR suggested causal effects of higher liver PDFF and cT1 on obesity-related traits, and inverse genetic associations between liver iron and coronary artery disease. MTAG identified seven additional loci (three for cT1, four for PDFF) not previously reported. CONCLUSIONS: This integrative imaging-genetics study reveals 13 potentially novel genes and several protein candidates implicated in hepatic steatosis, inflammation, and iron homeostasis. These findings enhance understanding of liver disease biology and may help identify new targets for early detection or treatment. IMPACT AND IMPLICATION: This large imaging-genetics study in over 37,000 people identifies genetic and protein factors linked to liver fat, fibroinflammation, and iron levels. It shows that higher liver fat and inflammation are associated with increased cardiometabolic risk, while higher liver iron appears inversely linked to risk of heart disease. These findings highlight molecular targets such as FADS1, FUT2, TMC4, RAB2B, and GPN1, which could inform future efforts to improve early detection or treatment of liver disease and its complications in people with obesity or metabolic syndrome.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316933","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 variations in AAK1 and ADAM17 associated with circulatory cytokines changes influence COVID-19 susceptibility and severity.","authors":"Amal Bouzid, Noha M Elemam, Habiba Alsafar, Thenmozhi Venkatachalam, Leen Eldoahji, Nour Halabi, Mohamed A Saleh, Iman M Talaat, Jalal Taneera, Nabil Sulaiman, Azzam A Maghazachi, Qutayba Hamid, Rifat Hamoudi, Maha Saber-Ayad","doi":"10.1186/s40246-026-00928-9","DOIUrl":"10.1186/s40246-026-00928-9","url":null,"abstract":"<p><strong>Background: </strong>The interplay between genetic factors and COVID-19 susceptibility and severity underscores the critical roles of genetic variations in the responses to the virus. Specifically, genetic variations in genes such as AAK1 and ADAM17 may influence the molecular pathways that determine how the virus enters cells and how the immune system responds, thereby affecting disease outcomes. Identifying these potential genetic variants clarifies individual responses to infectious diseases and helps aid in developing effective targeted therapeutic strategies.</p><p><strong>Methods: </strong>We performed targeted next-generation sequencing focusing on specific single-nucleotide variants (SNVs) in AAK1, ADAM17, and CD209 genes, which are implicated in the entry of SARS-CoV-2 into host cells. The study was conducted in a Middle Eastern cohort, comprising 96 COVID-19 patients with varying disease severities and 69 healthy controls. The correlation between the prevalence of the investigated genetic variants and the serum level of inflammatory cytokines within the studied cohort was also evaluated.</p><p><strong>Results: </strong>Our analysis revealed statistically significant differences in genetic variants between COVID-19 patients and healthy controls. Notably, a 5'UTR variant, rs12692386: chr2:9695906, A > G, in the ADAM17 gene showed a significant association (p = 0.039). Additionally, two variants in the AAK1 gene, an intronic variant chr2:69732672, C > A (p = 0.029) and a missense variant rs1275698668: chr2:69747984, G > C (p = 0.017), were identified, suggesting their potential role in influencing disease susceptibility and severity. The gender-stratified analysis between the two groups showed a significant difference in the AAK1-SNV-rs1275698668 (p = 0.027) in female susceptibility, suggesting a protective effect against SARS-CoV-2 infection. The AAK1-SNV-rs1275698668 showed a significant difference between the three severity groups (p = 0.045). Prediction in-silico tools suggest that 2:g.69747984G > C and 2:g.9,695,906 A > G have potential functional/regulatory impacts on the ADAM17 and AAK1 genes, respectively. Moreover, different correlation patterns between the identified genetic variants and inflammatory cytokine levels (including CD40 ligand, IL-1b, GM-CSF, and IL-4) were observed in COVID-19 patients.</p><p><strong>Conclusions: </strong>Our findings suggest potential genetic biomarkers in AAK1 and ADAM17 genes that could affect the disease severity and circulating cytokine levels in COVID-19 patients.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316913","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":"Children with suspected hereditary spastic paraplegia clearly benefit from whole exome analysis.","authors":"Dana Safka Brozkova, Jaroslava Paulasova Schwabova, Emilie Vyhnalkova, Petra Lassuthova, Alena Musilova, Ludmila Novotna, Jana Vasova, Anna Uhrova Meszarosova","doi":"10.1186/s40246-026-00935-w","DOIUrl":"10.1186/s40246-026-00935-w","url":null,"abstract":"<p><p>BACKGROUND: Establish a genetic diagnosis in patients referred for clinical suspicion of hereditary spastic paraplegia (HSP). The cohort of 134 paediatric patients was divided into three groups according to age at symptom onset: group A (0–5 years, n = 82), group B (5–10 years, n = 32), and group C (10–18 years, n = 20). Exome sequencing was followed by virtual panel evaluation of HSP associated genes. In patients with a negative result, full exome evaluation was subsequently performed. RESULTS: We established the genetic diagnosis in 31% of patients across all the groups, representing 41 index patients from 41 unrelated families. In the group A, the diagnostic yield increased by up to one-third when panel analysis was followed by full exome analysis, reaching 37%. In group B, 18% of patients were diagnosed using either a virtual panel or a combination of virtual panel and exome analysis. In group C, panel testing alone provided a 25% yield, with no additional benefit from exome evaluation. We confirmed 10 de novo variants comprising 19% of all detected variants, and except for one, all were detected in the group A. In the majority of solved patients, the diagnosis of HSP was confirmed by the detection of a pathogenic variant in an HSP-associated gene. However, in 32% of cases, the final diagnosis corresponded to a different rare neurological disorder, caused by a pathogenic variant in a gene associated with a condition other than HSP. Among the genetically solved patients with HSP our data suggest that autosomal dominant forms (82%) may be more common than autosomal recessive forms (18%) in paediatric patients in the Czech Republic. CONCLUSION: We have demonstrated that exome sequencing with virtual panel evaluation, followed by analysis of the full exome data according to HPO terms, is the most suitable approach, particularly for young paediatric patients.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305336","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":"Correction: A pan‑cancer analysis of the oncogenic and immunological roles of RGS5 in clear cell renal cell carcinomas based on in vitro experiment validation.","authors":"Ying Zhang, Huming Wang, Fang Dai, Ke He, Zhouting Tuo, Jinyou Wang, Liangkuan Bi, Xin Chen","doi":"10.1186/s40246-026-00938-7","DOIUrl":"10.1186/s40246-026-00938-7","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12937537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305306","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":"Challenges in functional validation and mechanistic interpretation of a novel LACC1 variant in familial juvenile arthritis.","authors":"Lin Yu, DuJiang Yang, Zhijun Ye, GuoYou Wang","doi":"10.1186/s40246-025-00865-z","DOIUrl":"10.1186/s40246-025-00865-z","url":null,"abstract":"<p><p>In their recent publication, Alblooshi et al. report the identification and preliminary functional analysis of a novel LACC1 variant, p.Asp220Asn, associated with familial juvenile idiopathic arthritis. While their study provides a valuable genetic association, this letter offers a critical appraisal to contextualize the findings and propose essential future directions. We contend that the functional characterization, while indicative of a loss-of-function, is insufficient to distinguish it from a potential dominant-negative mechanism, a distinction with paramount implications for genetic counseling. Furthermore, the observed clinical heterogeneity within the family remains mechanistically unaddressed; we propose that integrating systems-level approaches, such as transcriptomics and microbiome analysis, is crucial to move beyond mere description. Finally, the structural and metabolic consequences of the variant are underexplored. Employing molecular dynamics simulations and profiling mitochondrial metabolism in patient-derived cells could definitively link this genetic lesion to LACC1's emerging role in immunometabolism. This critique aims to elevate the impact of the initial discovery by mapping a pathway for transforming a genetic association into a profound pathophysiological understanding.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283452","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":"Outcomes of the national premarital genetic screening program for cystic fibrosis, homocystinuria, and spinal muscular atrophy in Qatar.","authors":"Sara Khalid AlMarzooqi, Reem Ibrahim Bux, Juby Ann Joy, Nazmul Islam, Tawfeg Ben-Omran, Ali Alawi Al-Hashimi, Moza Alkowari, Mashael Al-Shafai","doi":"10.1186/s40246-026-00937-8","DOIUrl":"10.1186/s40246-026-00937-8","url":null,"abstract":"<p><p>BACKGROUND: Premarital screening (PMS) programs have been increasingly implemented in various countries due to their potential to reduce the incidence of genetic conditions. In Qatar, a PMS program has been in place as a mandatory prerequisite for marriage since 2009 and its outcomes have not been explored. AIM: To assess the outcomes of the national premarital screening for cystic fibrosis (CF), Homocystinuria (HCU), and Spinal Muscular Atrophy (SMA) in Qatar and to provide insights and guide program’s improvements. METHODS: A retrospective population-based study on the PMS testing results for CF, HCU and SMA from 2009 to 2023. RESULTS: A total of 75,767 tests were initiated within this period with 99% of samples belonging to nationals. Testing for CF (47%) and HCU (48%) was similarly high compared to SMA which was significantly lower (5%), consistent with SMA’s optional screening status. The most common age at marriage was 20–30 years for females and 31–40 years for males. Carrier rates were highest for SMA (4.47%), followed by HCU (2.06%) and CF (1.46%). Among high-risk couples, 43.5% were positive for SMA, 30.5% for HCU, and 25.9% for CF. Consanguinity was reported in 46% of high-risk couples (where data was available) and was significantly associated with a higher likelihood of positive results (p < 0.001). More than half (53.6%) of high-risk couples continued with marriage. Among those, 85.2% had no affected children reported. Use of reproductive assistance with genetic testing was observed in 35.7% of positive couples, while 21.4% did not use it. Importantly, use of such technology was significantly associated with a reduced incidence of affected children (P = 0.024). CONCLUSION: Qatar’s PMS program was effective in reducing the incidence of the specified conditions. However, the absence of affected children among high-risk couples may be influenced by various factors. Therefore, while the results are encouraging, they should be interpreted with caution. Our findings highlight the need for enhanced risk counseling after positive results, and the need for public educational campaigns on the importance of premarital testing, the potential risks associated with consanguinity and the availability of reproductive technologies that may be utilized as a preventative option. </p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305323","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":"Response to Letter to the Editor.","authors":"Hiba Alblooshi, Najla Aljaberi","doi":"10.1186/s40246-025-00866-y","DOIUrl":"10.1186/s40246-025-00866-y","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283509","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":"Enhancing prostate cancer diagnosis: a machine learning-based biomarker approach.","authors":"Patricia Porras-Quesada, Alberto Ramírez-Mena, Verónica Arenas-Rodríguez, Fernando Vázquez-Alonso, Jesús Alcalá-Fdez, Beatriz Álvarez-González, Luis Javier Martínez-González, María Jesús Álvarez-Cubero","doi":"10.1186/s40246-026-00939-6","DOIUrl":"10.1186/s40246-026-00939-6","url":null,"abstract":"<p><p>BACKGROUND: The lack of reliable screening biomarkers for prostate cancer (PC) diagnosis makes tissue biopsy the gold-standard strategy. However, its frequent inconclusive results often lead to repeated procedures, increasing patient burden and healthcare costs. In this context, machine learning (ML) presents a novel approach for identifying gene signatures associated with tumor presence, offering a promising avenue for improved PC detection. Therefore, the present study explored the diagnostic potential of an ML-based gene signature and its applicability in tissue and plasma samples. METHODS: This study evaluated the clinical applicability of an ML-based algorithm developed using TCGA data (n = 608) and tested in an independent dataset (n = 349). The eleven candidate genes that contributed most to the predictive model were initially profiled by targeted RNA-Seq in prostate tissue validation cohort (n = 141) and further validated in replication tissue (n = 75) and plasma (n = 50) cohorts by qPCR and dPCR, respectively. RESULTS: Gene expression analysis in prostate tissue led to the identification of a six-gene signature (DLX1, TDRD1, AMACR, HPN, HOXC6, and OR51E2) with high diagnostic performance (AUC = 95.9%). Expression patterns supported the gene signature’s potential to identify false-negative cases and correctly classify inconclusive biopsy results. In plasma, AMACR demonstrated added diagnostic value as a non-invasive biomarker when integrated with clinical parameters (AUC = 93.21%). CONCLUSIONS: These findings demonstrate that our ML-based gene signature can accurately distinguish PC from non-tumoral tissue and resolve ambiguous biopsy results. Its integration alongside histopathology has the potential to reduce diagnostic uncertainty, improving PC early detection and guiding clinical decision-making. </p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283467","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":"Therapeutic rewiring of ceRNA networks: a computational pipeline for drug repurposing in acute kidney injury via circRNA-miRNA-mRNA axis disruption.","authors":"Ming Wang, Feng Gao","doi":"10.1186/s40246-026-00930-1","DOIUrl":"10.1186/s40246-026-00930-1","url":null,"abstract":"<p><p>This review synthesizes current evidence on competing endogenous RNA (ceRNA) regulation in acute kidney injury (AKI) and proposes a practical, reproducible framework for computationally guided drug repurposing that aims to rewire pathogenic circRNA–miRNA–mRNA axes. We summarize the ceRNA concept and its biological rationale in renal injury, anchored to foundational descriptions of the ceRNA hypothesis. Building on curated circRNA resources and drug–gene mapping platforms, we present and critically evaluate a five-stage computational framework: (1) multi-omics data mining and ceRNA triplet inference, (2) network pharmacology mapping to drug–gene resources, (3) RNA-aware molecular docking to candidate structured RNA motifs, (4) molecular dynamics (MD) refinement and rescoring, and (5) integrative prioritization with explicit experimental filters for renal safety and tractability. We synthesize methodological best practices and limitations for each stage, with particular attention to the emerging field of RNA-targeted small molecules and their experimental validation. Three illustrative case studies demonstrate how distinct repurposing logics (direct RNA engagement, network/miRNA modulation, pathway-level modulation) can be mapped onto this pipeline and what orthogonal assays are required to progress candidates from in silico nomination to biochemical and in vivo testing. The review concludes with a pragmatic experimental roadmap, clear caveats (RNA structural dynamics, cellular context dependency, miRNA redundancy), and proposals to integrate single-cell and systems-pharmacology approaches to improve replicability and translational potential. By collating the literature and proposing a transparent, stepwise framework with validation benchmarks, this review aims to generate testable, prioritized in-silico hypotheses for RNA-aware repurposing in AKI that require rigorous biochemical and preclinical validation before any consideration of clinical testing. Because AKI arises from multiple, biologically distinct etiologies (for example ischemia–reperfusion injury, sepsis, nephrotoxic injury such as cisplatin exposure, and obstructive causes), candidate drugs and circRNA/miRNA targets must be evaluated in etiology-matched cellular and animal models; the pipeline therefore explicitly recommends etiology-aware filtering and model selection to avoid overgeneralizing findings across all AKI types.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283462","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}