Genes & genomics最新文献

{"title":"Bacterial profile-based body fluid identification using a machine learning approach.","authors":"Sungmin Kim, Han Chul Lee, Jeong Eun Sim, Su Jeong Park, Hye Hyun Oh","doi":"10.1007/s13258-024-01594-8","DOIUrl":"10.1007/s13258-024-01594-8","url":null,"abstract":"<p><strong>Background: </strong>Identifying the origins of biological traces is critical for the reconstruction of crime scenes in forensic investigations. Traditional methods for body fluid identification rely on chemical, enzymatic, immunological, and spectroscopic techniques, which can be sample-consuming and depend on simple color-change reactions. However, these methods have limitations when residual samples are insufficient after DNA extraction.</p><p><strong>Objective: </strong>This study aimed to develop a method for body fluid identification by leveraging bacterial DNA profiling to overcome the limitations of the conventional approaches.</p><p><strong>Methods: </strong>Bacterial profiles were determined by sequencing the hypervariable region of the 16 S rRNA gene, using DNA metabarcoding of evidence collected from criminal cases. Amplicon sequence variants (ASVs) were analyzed to identify significant microbial patterns in different body fluid samples.</p><p><strong>Results: </strong>The bacterial profile-based method demonstrated high discriminatory power with a machine learning model trained using the naïve Bayes algorithm, achieving an accuracy of over 98% in classifying samples into one of four body fluid types: blood, saliva, vaginal secretion, and mixture traces of vaginal secretions and semen.</p><p><strong>Conclusion: </strong>Bacterial profiling enhances the accuracy and robustness of body fluid identification in forensic analysis, providing a valuable alternative to traditional methods by utilizing DNA and microbial community data despite the uncontrollable conditions. This approach offers significant improvements in the classification accuracy and practical applicability in forensic investigations.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"87-98"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete chloroplast genomes of three Polygala species and indel marker development for identification of authentic polygalae radix (Polygala tenuifolia).","authors":"Sumin Jeong, Jong Won Han, Yeseul Kim, Eunjeong Bak, Kyung Ho Ma, Jeong Hoon Lee, Jin Tae Jung, Inkyu Park","doi":"10.1007/s13258-024-01573-z","DOIUrl":"10.1007/s13258-024-01573-z","url":null,"abstract":"<p><strong>Background: </strong>In Korea, only Polygala tenuifolia is registered as Polygalae Radix in the pharmacopoeia, while in China, both P. tenuifolia and P. sibirica are used equally. Accurate identification of herbal medicines is crucial for their safety and efficacy, but commercial products are typically sold in dried form, making morphological distinction difficult. Therefore, a quick and accurate method to distinguish P. tenuifolia is necessary for proper utilization of medicinal herb.</p><p><strong>Objective: </strong>We aimed to identify specific molecular markers for P. tenuifolia to avoid confusion regarding its pharmacological efficacy and to evaluate the classification of Polygala using plastid phylogenetic data.</p><p><strong>Methods: </strong>We analyzed the sequences of three species distributed in Korea, P. tenuifolia, P. japonica, and P. sibirica, and assembled their chloroplast genome sequences. Comparative analysis revealed regions of local divergence, and six molecular markers were developed from these hotspots. Additionally, a phylogenetic tree was constructed to determine the phylogenetic positions of the three Polygala species.</p><p><strong>Results: </strong>The marker successfully identified the three Polygala species, and all commercial products and breeding lines tested were confirmed to be P. tenuifolia and recognized as authentic. Phylogenetic analysis revealed that P. tenuifolia forms a distinct cluster from P. sibirica and P. japonica.</p><p><strong>Conclusions: </strong>We determined the chloroplast genomes of the three Polygala species and performed phylogenetic tree analysis and marker development. Indel markers were developed to identify the critical herbal species, P. tenuifolia. This comprehensive study of the Polygala chloroplast genome provides useful information for P. tenuifolia identification.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"99-112"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression profiles of TNF-Alpha and HERV-K Env proteins in multiple types of colon and lung disease.","authors":"Eun-Ji Ko, Jee-Yeong Jeong, Sung Chul Bae, Hee-Jae Cha","doi":"10.1007/s13258-024-01585-9","DOIUrl":"10.1007/s13258-024-01585-9","url":null,"abstract":"<p><strong>Background: </strong>Human endogenous retroviruses (HERVs) were integrated into the human genome millions of years ago and have since proliferated to comprise about 8% of the human genome. For a long time, HERVs were thought to be remnants of ancient viruses, rendered inactive over the ages. However, recent studies have revealed that HERVs are involved in various diseases, including cancer. Notably, HERVs have been found to play a crucial role in immune responses and inflammatory processes, indicating their significant influence on the regulation of immune-related diseases.</p><p><strong>Objective: </strong>We reported in previous reports that HERV-K119 env Knockout (KO) and inflammatory response were associated. In this study, we identified the correlation between inflammatory disease and HERV-K Env and TNF-Alpha protein expression in multiple types of colon disease tissue and lung disease spectrum tissue.</p><p><strong>Methods: </strong>We performed Immunofluorescence (IF) using multiple types of colon disease and lung disease spectrum tissue microarray (TMAs) and compared and analyzed the patient clinical data provided.</p><p><strong>Results: </strong>As a result, we identified that the expression of HERV-K Env and TNF-Alpha proteins in certain colorectal inflammatory diseases and certain lung inflammatory diseases showed specific expression. And through the analysis of the clinical data provided, environmental factors could be identified.</p><p><strong>Conclusion: </strong>Our study demonstrates that the relationship between TNF-Alpha and HERV-K Env expression in inflammation disease and clinical significance of disease tissues.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"113-123"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and immunological role of LASP2 in clear cell renal cell carcinoma.","authors":"Libo Chen, Nanhui Chen, Zhouzhou Xie, Yuchen Xiao, Huiming Jiang","doi":"10.1007/s13258-024-01612-9","DOIUrl":"https://doi.org/10.1007/s13258-024-01612-9","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) represents a common renal carcinoma subtype influenced by the immune microenvironment. LIM and SH3 Protein 2 (LASP2), an actin-binding protein within the nebulin family, contributes to cellular immunity and adhesion mechanisms.</p><p><strong>Objective: </strong>This study aimed to clarify the immunological and prognostic relevance of LASP2 in ccRCC.</p><p><strong>Methods: </strong>Using clinical and expression data from TCGA, LASP2 expression levels were analyzed alongside clinicopathological features in ccRCC patients. Validation was conducted through real-world samples and tissue microarrays. Comprehensive analysis using online databases examined genetic mutations, DNA methylation patterns, and immune microenvironment characteristics. Gene set enrichment analysis (GSEA) provided insights into LASP2's potential mechanisms in ccRCC.</p><p><strong>Results: </strong>LASP2 expression was notably reduced and correlated with adverse clinicopathological features and prognosis in ccRCC patients. Prognostic associations were identified across multiple CpG DNA methylation sites. LASP2 levels showed significant correlations with immune cell infiltration and checkpoint genes, including PDCD1 and CTLA4. GSEA findings highlighted LASP2's enrichment within metabolic pathways and signaling networks, such as fatty acid metabolism, TGF-β signaling, and epithelial-mesenchymal transition.</p><p><strong>Conclusion: </strong>LASP2 emerged as an immune-associated biomarker linked to poorer survival outcomes in ccRCC, suggesting its potential as a novel anti-cancer target and prognostic indicator in ccRCC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis.","authors":"Yun Lei, Dan Shu, Jianyu Xia, Tao Zhang, He Wei","doi":"10.1007/s13258-024-01596-6","DOIUrl":"https://doi.org/10.1007/s13258-024-01596-6","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved.</p><p><strong>Objective: </strong>In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis.</p><p><strong>Methods: </strong>To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays.</p><p><strong>Results: </strong>Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells.</p><p><strong>Conclusions: </strong>The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide identification and expression profiling of the Wnt gene family in three abalone species.","authors":"Qian Zhang, Yangtao Fu, Yanyan Zhang, Hourong Liu","doi":"10.1007/s13258-024-01579-7","DOIUrl":"10.1007/s13258-024-01579-7","url":null,"abstract":"<p><strong>Background: </strong>The Wnt gene family plays pivotal roles in a variety of biological processes including cell proliferation and differentiation, apoptosis, and embryonic development. Identifying the Wnt signaling pathway in abalone could provide a basis for elucidating growth and development mechanisms and improving quality.</p><p><strong>Objective: </strong>To identify the number, protein physicochemical properties, gene structure, phylogenetic analysis, and expression profiles of the Wnt gene family in abalone.</p><p><strong>Methods: </strong>A comprehensive genome-wide analysis was performed to identify the Wnt gene family in the genomes of three abalone species (Haliotis discus hannai, H. rubra, and H. rufescens).</p><p><strong>Results: </strong>Ten single-copy Wnt genes were identified in each abalone species, suggesting that the number of Wnt genes was relatively conserved in Haliotis. Eight Wnt gene subfamilies, including Wnt1, Wnt4, Wnt5, Wnt6, Wnt7, Wnt10, Wnt16, and WntA, are present in all three species. Each abalone species contains two species-specific subfamilies (Wnt9 and Wnt11 in H. discus hannai, Wnt2 and Wnt11 in H. rubra, and Wnt2 and Wnt9 in H. rufescens), reflecting polymorphisms of the Wnt genes in Haliotis. Interestingly, gastropods are characterised by the loss of Wnt8, suggesting a potential evolutionary specificity in gastropods. As expected, Wnt3 is absent in all protostomes, including the abalone. In addition, spatio-temporal expression profiling revealed differential expression levels of the Wnt genes at different developmental stages and in different tissues of H. discus hannai. HdWnt5 and HdWntA might participate in several processes during larval development stages, including germ layer formation and body axis elongation. HdWnt5 may be involved in eye and tentacle development. HdWnt10 may be related to muscle development, and HdWnt6 may be involved in shell formation in abalone.</p><p><strong>Conclusion: </strong>To our knowledge, the results of this study, which is the first genome-wide investigation of the Wnt gene family in abalone, lay the groundwork for future research on the evolution and function of the Wnt gene family in Gastropoda.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1363-1374"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical report and genetic analysis of a Chinese family with retinitis pigmentosa 79 caused by a novel loss-of-function HK1 variant.","authors":"Xin Luo, Lu Wang, Daxi Xue","doi":"10.1007/s13258-024-01574-y","DOIUrl":"10.1007/s13258-024-01574-y","url":null,"abstract":"<p><strong>Background: </strong>Retinitis pigmentosa (RP) is a genetically heterogeneous disease. RP 79 has been associated with heterozygous variants of hexokinase 1 (HK1). Only two missense HK1 variants have been reported in 11 families.</p><p><strong>Objective: </strong>To discover the molecular pathogenic mechanism of RP and validate the biological harm of HK1 through in vitro experiments.</p><p><strong>Methods: </strong>We conducted a genetic analysis of a 3-year-old female patient with RP and her family. We also evaluated the ocular phenotypes caused by HK1 (the identified variant). Peripheral blood samples were collected from the patient, her parents, and her brother, and trio whole-exome sequencing was performed. A protein structure analysis was performed to assess the functional impact of the variant, and a mutant plasmid was constructed for the quantitative polymerase chain reaction (qPCR) and western blot (WB) analysis of the effects of the variant on transcription and protein translation.</p><p><strong>Results: </strong>The patient harbored the NM_000188.3: c.613del (p.Ala205Leufs*3) variant, which is a heterozygous variant of HK1. Sanger sequencing confirmed the presence of this variant in the patient; however, the patient's parents and brother had the wild-type variant. The protein structure analysis indicated that the variant resulted in a truncated protein caused by premature termination of amino acid coding. The qPCR results indicated that the variant may not have affected the transcription process. However, the WB analysis demonstrated that the mutant HK-1 protein was not expressed and that the wild-type group exhibited normal expression.</p><p><strong>Conclusions: </strong>Our patient had a loss-of-function (LoF) variant of HK1, which may be the genetic cause of typical features of RP that are observed at an early age. These findings expand the spectrum of HK1 variants and phenotypes and suggest that LoF variants of HK1 may represent a specific pathogenic mechanism of RP.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1437-1444"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Units containing telomeric repeats are prevalent in subtelomeric regions of a Mesorhabditis isolate collected from the Republic of Korea.","authors":"Seoyeon Kim, Jun Kim","doi":"10.1007/s13258-024-01576-w","DOIUrl":"10.1007/s13258-024-01576-w","url":null,"abstract":"<p><strong>Background: </strong>Mesorhabditis is known for its somatic genome being only a small portion of the germline genome due to programmed DNA elimination. This phenotype may be associated with the maintenance of telomeres at the ends of fragmented somatic chromosomes.</p><p><strong>Objective: </strong>To comprehensively investigate the telomeric regions of Mesorhabditis nematodes at the sequence level, we endeavored to collect a Mesorhabditis nematode in the Republic of Korea and acquire its highly contiguous genome sequences.</p><p><strong>Methods: </strong>We isolated a Mesorhabditis nematode and assembled its 108-Mb draft genome using both 6.3 Gb (53 ×) of short-read and 3.0 Gb (25 × , N50 = 5.7 kb) of nanopore-based long-read sequencing data. Our genome assembly exhibits comparable quality to the public genome of Mesorhabditis belari in terms of contiguity and evolutionary conserved genes.</p><p><strong>Results: </strong>Unexpectedly, our Mesorhabditis genome has many more interstitial telomeric sequences (ITSs), specifically subtelomeric ones, compared to the genomes of Caenorhabditis elegans and M. belari. Moreover, several subtelomeric sequences containing ITSs had 4-26 homologous sequences, implying they are highly repetitive. Based on this highly repetitive nature, we hypothesize that subtelomeric ITSs might have accumulated through the action of transposable elements containing ITSs.</p><p><strong>Conclusions: </strong>It still remains elusive whether these ITS-containing units are associated with programmed DNA elimination, but they may facilitate new telomere formation after DNA elimination. Our genomic resources for Mesorhabditis can aid in understanding how its distinct phenotypes have evolved.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1461-1472"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of single-cell RNA-seq and bulk RNA-seq revealed key genes for bone metastasis and chemoresistance in prostate cancer.","authors":"Hongai Bai, Zhenyue Li, Yueyue Weng, Facai Cui, Wenpu Chen","doi":"10.1007/s13258-024-01575-x","DOIUrl":"10.1007/s13258-024-01575-x","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a serious malignancy. The main causes of PCa aggravation and death are unexplained resistance to chemotherapy and bone metastases.</p><p><strong>Objective: </strong>This study aimed to investigate the molecular mechanisms associated with the dynamic processes of progression, bone metastasis, and chemoresistance in PCa.</p><p><strong>Methods: </strong>Through comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data, Gene Expression Omnibus (GEO) tumor progression and metastasis-related genes were identified. These genes were subjected to lasso regression modeling using the Cancer Genome Atlas (TCGA) database. Tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR (RT-qPCR) were used to evaluate osteoclast differentiation. CellMiner was used to confirm the effect of LDHA on chemoresistance. Finally, the relationship between LDHA and chemoresistance was verified using doxorubicin-resistant PCa cell lines.</p><p><strong>Results: </strong>7928 genes were identified as genes related to tumor progression and metastasis. Of these, 7 genes were found to be associated with PCa prognosis. The scRNA-seq and TCGA data showed that the expression of LDHA was higher in tumors and associated with poor prognosis of PCa. In addition, upregulation of LDHA in PCa cells induces osteoclast differentiation. Additionally, high LDHA expression was associated with resistance to Epirubicin, Elliptinium acetate, and doxorubicin. Cellular experiments demonstrated that LDHA knockdown inhibited doxorubicin resistance in PCa cells.</p><p><strong>Conclusions: </strong>LDHA may play a potential contributory role in PCa initiation and development, bone metastasis, and chemoresistance. LDHA is a key target for the treatment of PCa.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1445-1460"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kernel-based hierarchical structural component models for pathway analysis on survival phenotype.","authors":"Suhyun Hwangbo, Sungyoung Lee, Md Mozaffar Hosain, Taewan Goo, Seungyeoun Lee, Inyoung Kim, Taesung Park","doi":"10.1007/s13258-024-01569-9","DOIUrl":"10.1007/s13258-024-01569-9","url":null,"abstract":"<p><strong>Background: </strong>High-throughput sequencing, particularly RNA-sequencing (RNA-seq), has advanced differential gene expression analysis, revealing pathways involved in various biological conditions. Traditional pathway-based methods generally consider pathways independently, overlooking the correlations among them and ignoring quite a few overlapping biomarkers between pathways. In addition, most pathway-based approaches assume that biomarkers have linear effects on the phenotype of interest.</p><p><strong>Objective: </strong>This study aims to develop the HisCoM-KernelS model to identify survival phenotype-related pathways by accommodating complex, nonlinear relationships between genes and survival outcomes, while accounting for inter-pathway correlations.</p><p><strong>Methods: </strong>We applied HisCoM-KernelS model to the TCGA pancreatic ductal adenocarcinoma (PDAC) RNA-seq dataset, comprising 4,498 protein-coding genes mapped to 186 KEGG pathways from 148 PDAC samples. Kernel machine regression was used to model pathway effects on survival outcomes, incorporating hierarchical gene-pathway structures. Model parameters were estimated using the alternating least squares algorithm, and the significance of pathways was assessed through a permutation test.</p><p><strong>Results: </strong>HisCoM-KernelS identified several pathways significantly associated with pancreatic cancer survival, including those corroborated by previous studies. HisCoM-KernelS, especially with the Gaussian kernel, showed a better balance of detection rate and number of significant pathways compared to four other existing pathway-based methods: HisCoM-PAGE, Global Test, GSEA, and CoxKM.</p><p><strong>Conclusion: </strong>HisCoM-KernelS successfully extends pathway-based analysis to survival outcomes, capturing complex nonlinear gene effects and inter-pathway correlations. Its application to the TCGA PDAC dataset emphasizes its utility in identifying biologically relevant pathways, offering a robust tool for survival phenotype research in high-throughput sequencing data.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1415-1421"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}