Functional & Integrative Genomics最新文献

{"title":"The role of nanoparticles in transforming plant genetic engineering: advancements, challenges and future prospects","authors":"Neelam Rani,&nbsp;Kusum Kumari,&nbsp;Vinita Hooda","doi":"10.1007/s10142-025-01528-x","DOIUrl":"10.1007/s10142-025-01528-x","url":null,"abstract":"<div><p>Despite years of progress in biotechnology, altering the genetic makeup of many plant species, especially their plastids, remains challenging. The existence of a cell wall poses a significant obstacle to the effectual transportation of biomolecules. Developing efficient methods to introduce genes into plant cells and organelles without causing harm is an ongoing area of research. Traditional approaches like <i>Agrobacterium-</i>mediated transformation, biolistic particle delivery, electroporation and polyethylene glycol (PEG) transformation have shown some success but come with limitations like laborious, time-consuming and causing tissue damage. For instance, the <i>Agrobacterium</i> method can be applied only to the restricted host range, while PEG transformation and biolistic particle delivery are not very efficient. In contrast, nanotechnology made an appearance in the field of genetic engineering. Nanoparticles act as delivery vehicles for many cargos in animals. However, in plants, the application of nanocarriers for the delivery of biomolecules is still in its infant stage. Nonetheless, it holds immense potential for the future of plant biotechnology and genome editing.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995643","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":"High-throughput sequencing: a breakthrough in molecular diagnosis for precision medicine","authors":"Dipali Barku Dongare,&nbsp;Shaik Shireen Nishad,&nbsp;Sakshi Y. Mastoli,&nbsp;Shubhini A. Saraf,&nbsp;Nidhi Srivastava,&nbsp;Abhishek Dey","doi":"10.1007/s10142-025-01529-w","DOIUrl":"10.1007/s10142-025-01529-w","url":null,"abstract":"<div><p>High-resolution insights into the nucleotide arrangement within an organism’s genome are pivotal for deciphering its genetic composition, function, and evolutionary trajectory. Over the years, nucleic acid sequencing has been instrumental in driving significant advancements in genomics and molecular biology. The advent of high-throughput or next-generation sequencing (NGS) technologies has revolutionized whole genome sequencing, revealing novel and intriguing features of genomes, such as single nucleotide polymorphisms and lethal mutations in both coding and non-coding regions. These platforms provide a practical approach to comprehensively identifying and analyzing whole genomes with remarkable throughput, accuracy, and scalability within a short time frame. The resulting data holds immense potential for enhancing healthcare systems, developing novel and personalized therapies, and preparing for future pandemics and outbreaks. Given the wide array of available high-throughput sequencing platforms, selecting the appropriate technology based on specific needs is crucial. However, there is limited information regarding sample preparation, sequencing principles, and output data to facilitate a comparative evaluation of these platforms. This review details various NGS technologies and approaches, examining their advantages, limitations, and future potential. Despite being in their early stages and facing challenges, ongoing advancements in NGS are expected to yield significant future benefits. </p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995642","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":"Comparison of the rhizospheric soil bacteriomes of Oryza sativa and Solanum melongena crop cultivars reveals key genes and pathways involved in biosynthesis of ectoine, lysine, and catechol meta-cleavage","authors":"Manisha Mandal,&nbsp;Biswajit Ghosh,&nbsp;Shyamapada Mandal","doi":"10.1007/s10142-025-01536-x","DOIUrl":"10.1007/s10142-025-01536-x","url":null,"abstract":"<div><p>Rice (<i>Oryza sativa</i> L.), <i>Poaceae</i> family, forms staple diet of half of world’s population, and brinjal (<i>Solanum melongena</i> L.), an important solanaceous crop, are consumed worldwide. Rhizosphere research is gaining importance towards application of knowledge for improving productivity, sustainable agricultural practice, and rhizoremediation for nature restoration. While there are reports on rhizobacteriome of rice, studies comparing structural, functional and metabolomic traits of microbial communities in rhizospheres of rice and brinjal are not yet available. We demonstrated, in <i>Oryza sativa</i> (1144-Hybrid, Dhiren, Local Saran cultivars) and <i>Solanum melongena</i> (Jhiloria, Chandtara, Jotshna cultivars) rhizospheres from Malda, India, using integrated approach of 16 S ribosomal sequencing, shotgun metagenomics, and microbial metabolomics to decipher microbial diversity, association with soil physicochemical characteristics, key genes and pathways. Ectoine biosynthesis was significantly expressed in brinjal (Jhiloria), but not in rice rhizosphere. The dominant brinjal rhizobacteriome-specific bacteria comprised <i>Thermus</i> sp., <i>Petrobacter succinatimandens</i>, <i>Thermoanaerobacter</i> sp., and <i>Diaphorobacter</i> sp., that were involved in house-keeping functions including pentose phosphate pathway, biosynthesis of amino acids, lipopolysaccharide, and photosynthesis. The dominant bacteria unique to rice rhizobacteriome (Local Saran) consisted of <i>Aeromonas</i> sp., associated with catechol meta-cleavage, while <i>Clostridium</i> sp., <i>Faecalibacterium prausnitzii</i>, and <i>Roseburia</i> sp. were involved with lysine biosysnthesis in rice (1144-Hybrid). Our results imply novel information for improved breeding of brinjal specific cultivar with enhanced ectoine production associated with osmotic stress tolerance, rice specific cultivars with enhanced lysine production significant to human nutrition and catechol removal for the maintenance of environmental quality.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995697","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":"SUMMER: an integrated nanopore sequencing pipeline for variants detection and clinical annotation on the human genome","authors":"Renqiuguo Li,&nbsp;Hongyuan Chu,&nbsp;Kai Gao,&nbsp;Huaxia Luo,&nbsp;Yuwu Jiang","doi":"10.1007/s10142-025-01534-z","DOIUrl":"10.1007/s10142-025-01534-z","url":null,"abstract":"<div><p>Long-read sequencing has emerged as a transformative technology in recent years, offering significant potential for the molecular diagnosis of unresolved genetic disorders. Despite its promise, the comprehensive detection and clinical annotation of genomic variants remain intricate and technically demanding. We present SUMMER, an integrated and structured workflow specifically designed to process raw Nanopore sequencing reads. SUMMER facilitates an in-depth analysis of multiple variant types, including SNV, SV, short tandem repeat and mobile element insertion. For clinical applications, SUMMER employs SvAnna to prioritize SV candidates based on phenotype relevance and utilizes Straglr to provide reference distributions of non-pathogenic unit counts for 55 known pathogenic short tandem repeats. By addressing critical challenges in variant detection and annotation, SUMMER seeks to advance the clinical utility of long-read sequencing in diagnostic genomics. SUMMER is available on the web at https://github.com/carolhuaxia/summer.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01534-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritization of candidate genes regulating the dwarfness in rice by integration of whole-genome and transcriptome analyses","authors":"Gunasekaran Ariharasutharsan,&nbsp;Adhimoolam Karthikeyan,&nbsp;Seshadri Geetha,&nbsp;Muthurajan Raveendran,&nbsp;Ravi Lalitha,&nbsp;Latha Ananda-Lekshmi,&nbsp;Manoharan Akilan,&nbsp;Dhanalakshmi Veeraraj Sushmitharaj,&nbsp;Manickam Dhasarathan,&nbsp;Ramasamy Saraswathi,&nbsp;Paramasivam Arunachalam","doi":"10.1007/s10142-025-01532-1","DOIUrl":"10.1007/s10142-025-01532-1","url":null,"abstract":"<div><p>Dwarfism is a major trait for developing lodging-resistant rice cultivars. Gamma irradiation-induced mutagenesis has proven to be an effective method for generating dwarf rice mutants. In this research, we isolated a dwarf mutant from Anna R (4) in the M₂ generation and subsequently stabilized the trait through successive selfing of progeny across the M₃-M₇ generations. We then employed whole-genome re-sequencing (WGRS) and RNA sequencing (RNA-seq) analyses of Anna R (4) and the mutant (designated as ACM-20001) to elucidate the underlying mechanisms and identify candidate genes associated with dwarfness. Numerous genetic variations were identified between Anna (R) 4 and ACM-20001 through WGRS. In total, 2049 genetic variants, including 343 InDels and 1706 nonsynonymous SNPs, were identified across 697 genes. Additionally, RNA-seq analysis revealed 2,881 differentially expressed genes between the wild-type Anna (R) 4 and the mutant ACM-20001, with 1,451 genes up-regulated and 1,430 genes down-regulated in ACM-20001 compared to Anna (R) 4. By integrating WGRS and RNA-seq data with functional annotation analysis, we identified the most likely candidate genes (i.e., <i>Os02g0506400</i>, <i>Os05g0515200</i>, <i>Os06g0154200</i> and <i>Os08g0250900</i>) related to dwarfness. Quantitative real-time PCR analysis verified the expression of these genes. Collectively, our study provides valuable insights in to the genes and mechanisms underlying dwarfness in rice. Further studies are required to elucidate the roles of these candidate genes in dwarfness, which contribute to advancements rice breeding programs.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995084","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":"Genomics-assisted stacking of waxy1, opaque2, and crtRB1 genes for enhancing amylopectin in biofortified maize for industrial utilization and nutritional security","authors":"Subhra J. Mishra,&nbsp;Firoz Hossain,&nbsp;Rajkumar U. Zunjare,&nbsp;Rashmi Chhabra,&nbsp;Ashvinkumar Katral,&nbsp;Ikkurti Gopinath,&nbsp;Vinay Bhatt,&nbsp;Govinda Rai Sarma,&nbsp;Zahirul A. Talukder,&nbsp;Ravindra K. Kasana,&nbsp;Elangbam L. Devi,&nbsp;Konsam Sarika,&nbsp;Brijesh K. Mehta,&nbsp;Satish K. Guleria,&nbsp;Jitender Kumar,&nbsp;Vignesh Muthusamy","doi":"10.1007/s10142-024-01523-8","DOIUrl":"10.1007/s10142-024-01523-8","url":null,"abstract":"<div><p>Waxy maize is highly preferred diet in developing countries due to its high amylopectin content. Enriching amylopectin in biofortified maize meets food security and fulfils the demand of rising industrial applications, especially bioethanol. The mutant <i>waxy1</i> (<i>wx1</i>) gene is responsible for increased amylopectin in maize starch, with a wide range of food and industrial applications. Conventional maize has a modest amount of amylopectin (70–75% of starch), but waxy maize, with favourable <i>wx1</i> allele, has ~ 95–100% amylopectin. In this study, the <i>wx1</i> allele was introgressed into the multi-nutrient-rich maize parental inbreds (PMI-PV9 and PMI-PV5) of APQH8, a multi-nutrient rich maize hybrid having high lysine, tryptophan, and provitamin-A nutritionally superior over the traditional hybrids. Gene-specific markers specific for <i>o2</i> and <i>crtRB1</i> were employed to select desirable gene segregants from BC₁F₁, BC₂F₁, and BC₂F₂. Background selection was employed with &gt; 90 SSR markers. Selected backcross progenies showed high recovery of recurrent parent genomes (RPG: 94.8–96.8%). The reconstituted waxy hybrids exhibited an increase in amylopectin (mean: 98.4%) compared to the original hybrid (mean: 72.7%). The reconstituted hybrids also recorded enhanced lysine (mean: 0.382%), tryptophan (mean: 0.092%), and provitamin-A (mean: 10.36 ppm), respectively, than normal maize, however similar to the original hybrid with high lysine: 0.330%, tryptophan: 0.079% and provitamin-A: 10.42 ppm. Furthermore, MAS-derived genotypes showed similar agro-morphological traits and grain yield. These biofortified waxy maize hybrids, rich in provitamin-A, lysine, and tryptophan with enhanced amylopectin hold great potential in diverse industrial applications and nutritional security.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994919","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":"Overexpression of FTO alleviates traumatic brain injury induced posttraumatic epilepsy by upregulating NR4A2 expression via m6A demethylation","authors":"Manjun Xiao,&nbsp;Xiaohong Wang,&nbsp;Enhua Xiao,&nbsp;Qianwen Ming","doi":"10.1007/s10142-024-01522-9","DOIUrl":"10.1007/s10142-024-01522-9","url":null,"abstract":"<div><p>Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI). Although FTO has been reported as a possible intervention target of TBI, its precise roles in the PTE remain incompletely understood. Here we used mild or serious mice TBI model to probe the role and molecular mechanism of FTO in PTE. The results of electroencephalography showed that frequency of epilepsy in serious TBI model mice was more obvious. Using quantitative PCR (qPCR) and western blot analysis, we demonstrated that FTO and NR4A2 were downregulated, while m6A level of NR4A2 mRNA was upregulated in the hippocampus of serious TBI mice. Functionally, FTO overexpression was found to reduce epilepsy susceptibility, blood–brain barrier (BBB) disruption and neuronal damage in TBI mice, suggested a role for FTO in PTE. In addition, RNA-binding protein immunoprecipitation and dual-luciferase assay experiment showed that NR4A2 was a target of FTO, and FTO upregulated NR4A2 expression through m6A-YTHDF2 manner. Furthermore, the molecular and histological changes caused by FTO overexpression are markedly reversed by NR4A2 knockdown in TBI mice. Collectively, our results demonstrate that FTO alleviates epilepsy susceptibility and brain injury after TBI by mediating epigenetic up-regulation of NR4A2, which implicates it as a potential therapeutic target for PTE.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995492","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":"Role of long non-coding RNAs and natural products in prostate cancer: insights into key signaling pathways","authors":"Ahmed S. Doghish,&nbsp;Sherif S. Abdel Mageed,&nbsp;Mohamed Bakr Zaki,&nbsp;Mai A. Abd-Elmawla,&nbsp;Ghadir A. Sayed,&nbsp;Abdulrahman Hatawsh,&nbsp;Nora M. Aborehab,&nbsp;Rewan Moussa,&nbsp;Osama A. Mohammed,&nbsp;Mustafa Ahmed Abdel-Reheim,&nbsp;Hanan Elimam","doi":"10.1007/s10142-025-01526-z","DOIUrl":"10.1007/s10142-025-01526-z","url":null,"abstract":"<div><p>Prostate cancer (PC) ranks among the most prevalent cancers in males. Recent studies have highlighted intricate connections between long non-coding RNAs (lncRNAs), natural products, and cellular signaling in PC development. LncRNAs, which are RNA transcripts without protein-coding function, influence cell growth, programmed cell death, metastasis, and resistance to treatments through pathways like PI3K/AKT, WNT/β-catenin, and androgen receptor signaling. Certain lncRNAs, including HOTAIR and PCA3, are associated with PC progression, with potential as diagnostic markers. Natural compounds, such as curcumin and resveratrol, demonstrate anticancer effects by targeting these pathways, reducing tumor growth, and modulating lncRNA expression. For instance, curcumin suppresses HOTAIR levels, hindering PC cell proliferation and invasion. The interaction between lncRNAs and natural compounds may open new avenues for therapy, as these substances can simultaneously impact multiple signaling pathways. These complex interactions offer promising directions for developing innovative PC treatments, enhancing diagnostics, and identifying new biomarkers for improved prevention and targeted therapy. This review aims to map the multifaceted relationship among natural products, lncRNAs, and signaling pathways in PC pathogenesis, focusing on key pathways such as AR, PI3K/AKT/mTOR, WNT/β-catenin, and MAPK, which are crucial in PC progression and therapy resistance. Regulation of these pathways by natural products and lncRNAs could lead to new insights into biomarker identification, preventive measures, and targeted PC therapies.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995268","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":"Elucidating circRNA-miRNA-mRNA competing endogenous regulatory RNA network during leaf rust pathogenesis in wheat (Triticum aestivum L.)","authors":"Umang Kumar Dhandhanya,&nbsp;Uzma Afreen,&nbsp;Shailendra Kumar Jha,&nbsp;Kunal Mukhopadhyay,&nbsp;Manish Kumar","doi":"10.1007/s10142-024-01520-x","DOIUrl":"10.1007/s10142-024-01520-x","url":null,"abstract":"<div><p>Advancements in bioinformatic tools and breakthroughs in high throughput RNA sequencing have unveiled the potential role of non-coding RNAs in influencing the overall expression of disease-responsive genes. Owing to the increasing need to develop resilient crop varieties against environmental constraints, our study explores the functional relationship of various non-coding RNAs in wheat during leaf rust pathogenesis. MicroRNAs (miRNAs) and circular RNAs (circRNAs) were retrieved from SAGE and RNA-Seq libraries, respectively, in the susceptible (HD2329) and resistant (HD2329 + <i>Lr28</i>) wheat Near-Isogenic Lines (NILs). Here we explored the previously published circRNAs for their differential expression and correlated the data with the differentially expressed miRNAs (DEMs) through various in silico methods to acquire the target miRNAs of circRNAs and the downstream target mRNAs of miRNAs. Finally, a competing endogenous RNA (ceRNAs) regulatory network was constructed and validated through RT-qPCR method. We have identified the ceRNA regulatory network of four differentially expressed circRNAs (DECs) and five DEMs to highlight their crucial roles in the robust enhancement of the temporal expression profiles of five defense responsive genes (mRNAs) in wheat NILs against leaf rust infection. The study confirms the synergistic expression of circRNAs and mRNAs with an antagonistic correlation with the expression profile of the corresponding miRNAs. The vital role of leaf rust-resistant gene <i>Lr28</i> has also been highlighted for driving the efficiency of the circRNAs to upregulate target gene expression. Thus, understanding the circRNA-miRNA-target gene interaction during leaf rust pathogenesis can help to identify stress-specific regulatory biomarkers to enhance defense responses in wheat for improved resilience through multi-omics integration of transcriptomics, proteomics and metabolomics.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995184","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":"Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base","authors":"Traci L. Parry,&nbsp;L. Anne Gilmore,&nbsp;Andy V. Khamoui","doi":"10.1007/s10142-024-01524-7","DOIUrl":"10.1007/s10142-024-01524-7","url":null,"abstract":"<div><p>Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers. Tumor proteins having significant pan-cancer associations with muscle were referenced against secretome proteins secreted to blood from the Human Protein Atlas, then verified as increased in paired tumor vs. normal tissues in pan-cancer manner. This workflow revealed seven secreted proteins from cancers afflicting kidneys, head and neck, lungs and pancreas that classified as protein-binding activity modulator, extracellular matrix protein or intercellular signaling molecule. Concordance of these biomarkers with validated molecular signatures of cachexia and senescence supported relevance to muscle and cachexia disease biology, and high tumor expression of the biomarker set associated with lower overall survival. In this article, we discuss avenues by which skeletal muscle and cachexia may be regulated by these candidate pan-cancer proteins secreted to blood, and conceptualize a strategy that considers them collectively as a biomarker signature with potential for refinement by data analytics and radiogenomics for predictive testing of future risk in a non-invasive, blood-based panel amenable to broad uptake and early management.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976484","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}