High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging ...High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leu...Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.展开更多
Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that i...Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that involve multiple quantitative trait loci and environmental factors(Liu and Yan,2019;Tam et al.,2019).Despite recent advancements in GWAS tools such as GAPIT3(Tang et al.,2016)and HAPPI GWAS(Slaten et al.,2020),which have facilitated the exploration of relationships between molecular and phenotypic traits,these tools still adhere to conventional GWAS designs and exhibit limited capabilities in establishing associations across multi-omics layers.展开更多
Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with...Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with oral paliperidone were analyzed through genotyping,mass spectrometry proteomic,and metabolomic profiling to explore underlying markers and mechanisms of antipsychotic efficacy.Machine learning analysis identified 20 proteins and 20 metabolites at baseline predictive of treatment response.Proteomic and metabolomic models achieved a cross-site mean AUC of 0.923 and 0.816,respectively.A multi-omics ensemble model achieved 0.941.GWAS and differential analyses identified 32 loci(P<5×10-5),83 proteins,and 31 metabolites associated with efficacy(P<0.05).Trans-omics analysis of these efficacy-related molecules across three omic layers highlighted glycerophospholipid metabolism(P=3.25×10-5)and sphingolipid metabolism(P=0.039).Key molecules within these pathways exhibited a consistent direction of effect in regulating phosphatidylcholine(PC)and sphingomyelin(SM)metabolism,and higher PC and SM levels were found to correlate with better efficacy.These associations were further genetically validated using polygenic risk scores in two independent cohorts(2281 and 449 patients,respectively).In conclusion,multi-omics modeling is able to accurately identify antipsychotic efficacy,and higher PC and SM levels correlate with better antipsychotic efficacy,suggesting that variations in phospholipid metabolism may underlie the response to antipsychotics.展开更多
Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adeno...Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.展开更多
Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar...Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar yield is limited by restricted genetic diversity and an exceptionally complex genome.This genetic complexity stems from the polyploid nature of sugarcane,which arose from a historical hybridization between Saccharum officinarum and Saccharum spontaneum.展开更多
To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]Th...To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]The presence of AD significantly impairs patient quality of life and imposes substantial economic burdens on society.In recent years,the potential link between AD and lymphoma has attracted considerable attention from researchers and clinicians.Lymphoma,a malignancy of the lymphatic system,poses significant health risks due to its high mortality potential.[2]However,observational studies investigating the potential correlation between AD and lymphoma have yielded inconsistent results.Consequently,the association between AD and lymphoma remains controversial and warrants further investigation.展开更多
Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,...Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,a huge challenge has also been posed for researchers to deal with the dramatically increasing amount of multi-omics data.展开更多
Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(...Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(HGsc).These alterations often include BRCA1/2 and TP53 mutations,and their impact is further assessed through homologous recombination deficiency(HRD)derived from genomic instability markers such as loss of heterozygosity and telomeric imbalance.展开更多
Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi...Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.展开更多
Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied wi...Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.展开更多
The Tibetan antelope(Pantholops hodgsonii),blue sheep(Pseudois nayaur),and Tibetan sheep(Ovis aries)are the dominant small ruminants in the Three-River-Source National Park(TRSNP).However,knowledge about the associati...The Tibetan antelope(Pantholops hodgsonii),blue sheep(Pseudois nayaur),and Tibetan sheep(Ovis aries)are the dominant small ruminants in the Three-River-Source National Park(TRSNP).However,knowledge about the association between gut microbiota and host adaptability remains poorly understood.Herein,multi-omics sequencing approaches were employed to investigate the gut microbiota-mediated forage adaption in these ruminants.The results revealed that although wild ruminants(WR)of P.hodgsoni and P.nayaur were faced with severe foraging environments with significantly low vegetation coverage and nutrition,the apparent forage digestibility of dry matter,crude protein,and acid detergent fiber was significantly higher than that of O.aries.The 16s rRNA sequencing showed that the gut microbiota in WR underwent convergent evolution,and alpha diversity in these two groups was significantly higher than that in O.aries.Moreover,indicator species,including Bacteroidetes and Firmicutes,exhibited positive relationships with apparent forage digestibility,and their relative abundances were enriched in the gut of WR.Enterotype analysis further revealed that enterotype 1 belonged to WR,and the abundance of fatty acid synthesis metabolic pathway-related enzyme genes was significantly higher than enterotype 2,represented by O.aries.Besides,the metagenomic analysis identified 14 pathogenic bacterial species,among which 10 potentially pathogenic bacteria were significantly enriched in the gut microbiota of O.aries.Furthermore,the cellulolytic strains and genes encoding cellulase and hemicellulase were significantly enriched in WR.In conclusion,our results provide new evidence of gut microbiota to facilitate wildlife adaption in severe foraging environments of the TRSNP,China.展开更多
Exercise is widely recognized for its extensive health benefits,ranging from cardiovascular protection to improved metabolic function and immune regulation.However,exercise-induced physiological adaptations are highly...Exercise is widely recognized for its extensive health benefits,ranging from cardiovascular protection to improved metabolic function and immune regulation.However,exercise-induced physiological adaptations are highly dependent on duration and frequency(Sanford et al.,2020).While acute exercise(AE)rapidly activates metabolic and immune responses(Mo Tr PAC Study Group et al.,2024),long-term exercise(LE)brings profound and systemic benefits,such as enhanced immunity,tissue regeneration,improved neuroplasticity,and cognitive function,optimized skeletal muscle metabolism and insulin sensitivity,and alleviation of chronic inflammation(De Miguel et al.,2021).展开更多
Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellula...Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellular and niche events at the precancerous tipping point of early gastric cancer(EGC),we aimed to develop more precise screening tools and design targeted interventions to prevent malignant transformation at this stage.We utilized our AI models to integrate spatial multimodal data from nine EGC endoscopic submucosal dissection(ESD)samples(covering sequential stages from normal to cancer),construct a spatial-temporal profile of disease progression,and identify a critical tipping point(PMC_P)characterized by an immune-suppressive microenvironment during early cancer development.At this stage,inflammatory pit mucous cells with stemness(PMC_2)interact with fibroblasts via NAMPT→ITGA5/ITGB1 and with macrophages via AREG→EGFR/ERBB2 signaling,fostering cancer initiation.We established gastric precancerous cell lines and organoids to demonstrate that NAMPT and AREG promote cellular proliferation in vitro.Furthermore,in the transgenic CEA-SV40 mouse model,targeting AREG and/or NAMPT disrupted key cell interactions,inhibited the JAK-STAT,MAPK,and NFκB pathways,and reduced PD-L1 expression,which was also confirmed by western blot in vitro.These interventions delayed disease progression,reversed the immunosuppressive microenvironment,and prevented malignant transformation.Clinical validation was conducted using endoscopically resected EGC specimens.Our study provides a precise spatiotemporal depiction of EGC development and identifies novel diagnostic markers and therapeutic targets for early intervention.展开更多
Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibi...Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibitors,though resistance often develops[1].Immunotherapy has been explored for advanced or resistant ALK-positive NSCLC,but immune checkpoint blockade(ICB)treatments have shown limited clinical benefits[1].展开更多
Cancer is a complex and heterogeneous disease characterized by various genetic and epigenetic alterations.Early diagnosis,accurate subtyping,and staging are essential for effective,personalized treatment and improved ...Cancer is a complex and heterogeneous disease characterized by various genetic and epigenetic alterations.Early diagnosis,accurate subtyping,and staging are essential for effective,personalized treatment and improved survival rates.Traditional diagnostic methods,such as biopsies,are invasive and carry operational risks that hinder repeated use,underscoring the need for noninvasive and personalized alternatives.In response,this study integrates transcriptomic data into human genome-scale metabolic models(GSMMs)to derive patient-specific flux distributions,which are then combined with genomic,proteomic,and fluxomic(JX)data to develop a robust multi-omic classifier for lung cancer subtyping and early diagnosis.The JX classifier is further enhanced by analyzing heterogeneous datasets from RNA sequencing and microarray analyses derived from both tissue samples and cell culture experiments,thereby enabling the identification of key marker features and enriched pathways such as lipid metabolism and energy production.This integrated approach not only demonstrates high performance in distinguishing lung cancer subtypes and early-stage disease but also proves robust when applied to limited pancreatic cancer data.By linking genotype to phenotype,GSMM-driven flux analysis overcomes challenges related to metabolome data scarcity and platform variability by proposing marker processes and reactions for further investigation,ultimately facilitating noninvasive diagnostics and the identification of actionable biomarkers for targeted therapeutic intervention.These findings offer significant promise for streamlining clinical workflows and enabling personalized therapeutic strategies,and they highlight the potential of our versatile workflow for unveiling novel biomarker landscapes in less studied diseases.展开更多
Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidpto...Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.展开更多
The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transform...The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transformed the diagnosis,treatment,and care of patients.AI-powered solutions are enhancing the efficiency and accuracy of healthcare delivery by demonstrating exceptional skills in personalized medicine,early disease detection,and predictive analytics.Furthermore,telemedicine and remote patient monitoring systems have overcome geographical constraints,offering easy and accessible healthcare services,particularly in underserved areas.Wearable technology,the Internet of Medical Things,and sensor technologies have empowered individuals to take an active role in tracking and managing their health.These devices facilitate real-time data collection,enabling preventive and personalized care.Additionally,the development of 3D printing technology has revolutionized the medical field by enabling the production of customized prosthetics,implants,and anatomical models,significantly impacting surgical planning and treatment strategies.Accepting these advancements holds the potential to create a more patient-centered,efficient healthcare system that emphasizes individualized care,preventive care,and better overall health outcomes.This review's novelty lies in exploring how these technologies are radically transforming the healthcare industry,paving the way for a more personalized and effective healthcare for all.It highlights the capacity of modern technology to revolutionize healthcare delivery by addressing long-standing challenges and improving health outcomes.Although the approval and use of digital technology and advanced data analysis face scientific and regulatory obstacles,they have the potential for transforming translational research.as these technologies continue to evolve,they are poised to significantly alter the healthcare environment,offering a more sustainable,efficient,and accessible healthcare ecosystem for future generations.Innovation across multiple fronts will shape the future of advanced healthcare technology,revolutionizing the provision of healthcare,enhancing patient outcomes,and equipping both patients and healthcare professionals with the tools to make better decisions and receive personalized treatment.As these technologies continue to develop and become integrated into standard healthcare practices,the future of healthcare will probably be more accessible,effective,and efficient than ever before.展开更多
Colorectal cancer(CRC)continues to be the third most frequently diagnosed cancer,and the second leading cause of cancer-related mortality.Several non-invasive biomarkers have emerged,but only a few have been incorpora...Colorectal cancer(CRC)continues to be the third most frequently diagnosed cancer,and the second leading cause of cancer-related mortality.Several non-invasive biomarkers have emerged,but only a few have been incorporated into clinical practice due to the lack of sensitivity.1 Research on the epigenome has unveiled potential clinical applications for diagnosis and therapy response.2,3 Particularly,recent evidence suggests a novel role of RNA methylation in the development of CRC,4 revealing an overall RNA m6A hypomethylation.5 However,our understanding of their contribution to CRC remains limited.展开更多
文摘High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by the Multi-Center Clinical Research Project of the National Clinical Research Center for Geriatric Diseases(No.NCRCG-PLAGH-20230010)the Key Military Health Project(No.23BJZ25).
文摘Chronic myelomonocytic leukemia(CMML),a rare and malignant hematologic disorder,is classified as a myelodysplastic/myeloproliferative neoplasm(MDS/MPN).1 It poses a significant risk of progression to acute myeloid leukemia and is generally associated with a poor prognosis.2 CMML predominantly affects older adults,and treatment often involves demethylation therapy tailored to the patient's age and overall health.3 However,the complete remission rate for patients with CMML undergoing demethylation therapy is<20%and is frequently accompanied with severe side effects.1 Here,we discuss the case of an 84-year-old male diagnosed with CMML 6 years earlier,who experienced significant bone marrow suppression following demethylation therapy.By integrating multiomics data with bioinformatics,we developed and applied a novel approach of trimetinib monotherapy.This treatment resulted in notable improvements in hematopoietic function and overall quality of life,offering a promising strategy for managing CMML.
基金supported by the Biological Breeding-National Science and Technology Major Project(2023ZD0407501 to X.W.)the Pinduoduo-China Agricultural University Research Fund(PC2024A01003 to X.W.)+3 种基金the National Key Research and Development Program of China(2023YFF1000100 to J.Y.)the National Natural Science Foundation of China(32341036 to J.Y.)the Hebei Provincial Science and Technology Plan Project Modern Breeding Industry Science and Technology Innovation Special Project(21326316D and 21326302D to J.Z.)the S&T Program of Hebei(215A7612D to J.Z.).
文摘Dear Editor,Genome-wide association studies(GWAS)are pivotal genetic methodologies for identifying genomic regions associated with specific traits in crops.However,they often face challenges with complex traits that involve multiple quantitative trait loci and environmental factors(Liu and Yan,2019;Tam et al.,2019).Despite recent advancements in GWAS tools such as GAPIT3(Tang et al.,2016)and HAPPI GWAS(Slaten et al.,2020),which have facilitated the exploration of relationships between molecular and phenotypic traits,these tools still adhere to conventional GWAS designs and exhibit limited capabilities in establishing associations across multi-omics layers.
基金supported by the National Natural Science Foundation of China(82330042,82441005,82501802,82301687,82571710)National Key R&D Program of China(2023YFE0119400)+6 种基金Capital’s Funds for Health Improvement and Research(2024-1-4111)STI2030-Major Projects(2021ZD0200702)Beijing Municipal Health Commission Research Ward Programme(3rd batch)Beijing Nova Program(20230484425)China Postdoctoral Science Foundation(2024M760141)National Postdoctoral Program for Innovative Talents(BX20240029)Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation,the Fundamental Research Funds for the Central Universities(BMU2025YFJHPY044).
文摘Nearly 30%of patients with schizophrenia respond inadequately to current antipsychotics,with unclear markers and mechanisms of antipsychotic efficacy.A total of 208 patients with schizophrenia treated for 6 weeks with oral paliperidone were analyzed through genotyping,mass spectrometry proteomic,and metabolomic profiling to explore underlying markers and mechanisms of antipsychotic efficacy.Machine learning analysis identified 20 proteins and 20 metabolites at baseline predictive of treatment response.Proteomic and metabolomic models achieved a cross-site mean AUC of 0.923 and 0.816,respectively.A multi-omics ensemble model achieved 0.941.GWAS and differential analyses identified 32 loci(P<5×10-5),83 proteins,and 31 metabolites associated with efficacy(P<0.05).Trans-omics analysis of these efficacy-related molecules across three omic layers highlighted glycerophospholipid metabolism(P=3.25×10-5)and sphingolipid metabolism(P=0.039).Key molecules within these pathways exhibited a consistent direction of effect in regulating phosphatidylcholine(PC)and sphingomyelin(SM)metabolism,and higher PC and SM levels were found to correlate with better efficacy.These associations were further genetically validated using polygenic risk scores in two independent cohorts(2281 and 449 patients,respectively).In conclusion,multi-omics modeling is able to accurately identify antipsychotic efficacy,and higher PC and SM levels correlate with better antipsychotic efficacy,suggesting that variations in phospholipid metabolism may underlie the response to antipsychotics.
基金supported by Henan Provincial Key Laboratory of Medicine and Henan Provincial Clinical Medical Research Center for Respiratory Diseases.
文摘Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA0450102 and XDA0460405)the Biological Breeding-National Science and Technology Major Project(2022ZD04017)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y2021038)the Informatization Plan of Chinese Academy of Sciences[CAS-WX2024GC-0602]。
文摘Dear Editor,As the predominant source of 80%of global sugar production,sugarcane is not only a critical pillar of food security but also an indispensable component of agricultural economies worldwide.However,its sugar yield is limited by restricted genetic diversity and an exceptionally complex genome.This genetic complexity stems from the polyploid nature of sugarcane,which arose from a historical hybridization between Saccharum officinarum and Saccharum spontaneum.
基金supported by grants from the National Key R&D Program of China(Nos.2022YFC3602002 and 2024YFF0507404)National High Level Hospital Clinical Research Funding(Nos.2022-NHLHCRF-LX-02-03 and 2023-NHLHCRF-YXHZ-ZRZD-06).
文摘To the Editor:Atopic dermatitis(AD)is a chronic inflammatory skin condition marked by recurrent eczematous lesions and intense pruritus,affecting approximately 15–20%of children and up to 10%of adults worldwide.[1]The presence of AD significantly impairs patient quality of life and imposes substantial economic burdens on society.In recent years,the potential link between AD and lymphoma has attracted considerable attention from researchers and clinicians.Lymphoma,a malignancy of the lymphatic system,poses significant health risks due to its high mortality potential.[2]However,observational studies investigating the potential correlation between AD and lymphoma have yielded inconsistent results.Consequently,the association between AD and lymphoma remains controversial and warrants further investigation.
基金supported by the National Natural Science Foundation of China(32171917)the Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(2021C02064-3)+1 种基金the Shenzhen Science and Technology Program(KQTD20230301092839007)the China Agricultural Research System(CARS-05).
文摘Dear Editor,The rapid development of barley genomics research in recent years has greatly enhanced our understanding of the molecular regulatory mechanisms underlying the complex characters(Jiang et al.,2025).However,a huge challenge has also been posed for researchers to deal with the dramatically increasing amount of multi-omics data.
基金supported by the National Natural Science Foundation of China(No.81472441 to X.Chen)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(No.SJCX22_0657 to L.Ruan).
文摘Key genetic alterations in DNA repair influence the effectiveness of treatments like platinum-based chemotherapy and poly(ADP-ribose)polymerase inhibitors in ovarian cancer,particularly in high-grade serous carcinoma(HGsc).These alterations often include BRCA1/2 and TP53 mutations,and their impact is further assessed through homologous recombination deficiency(HRD)derived from genomic instability markers such as loss of heterozygosity and telomeric imbalance.
基金supported by the Biological Breeding-Major Projects(2023ZD04076)the Pinduoduo-China Agricultural University Research Fund(PC2023B01012)+1 种基金the 2115 Talent Development Program of China Agricultural University,the National Natural Science Foundation of China(32201718)the Science and Technology Demonstration Project of Shandong Province(2024SFGC0402).
文摘Dear Editor,Multi-omics association analysis is a key method in crop germplasm research,helping to elucidate the regulatory mechanisms of agronomic traits(Liu et al.,2020;Liang et al.,2021).However,most existing multi-omics association studies focus on omics data under a single condition,posing challenges in identifying stress-related agronomically important genes.This difficultymainly arises fromthe increased complexity ofmulti-omics analyseswhen comparing control and stress conditions.
基金supported by The Brain Tumour Charity(grant number GN-000707)supported by DKTK JF Upgrade Next Gen LOGGIC(B310-JF-LOGGIC-MDE)supported by the DFG through a Heisenberg professorship(BR 3662/5-1)and SFB-1479 Oncoescape-Project ID:441891347(P14)。
文摘Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.
基金supported by the Youth Fund Project of the National Natural Science Foundation of China(32100100)the Joint Grant from the Chinese Academy of Sciences-People’s Government of Qinghai Province on Sanjiangyuan National Park(LHZX-2022-02)+1 种基金the Youth Innovation Promotion Association,Chinese Academy of Sciencesthe National Science Foundation of Qinghai Province(2022-ZJ-943Q).
文摘The Tibetan antelope(Pantholops hodgsonii),blue sheep(Pseudois nayaur),and Tibetan sheep(Ovis aries)are the dominant small ruminants in the Three-River-Source National Park(TRSNP).However,knowledge about the association between gut microbiota and host adaptability remains poorly understood.Herein,multi-omics sequencing approaches were employed to investigate the gut microbiota-mediated forage adaption in these ruminants.The results revealed that although wild ruminants(WR)of P.hodgsoni and P.nayaur were faced with severe foraging environments with significantly low vegetation coverage and nutrition,the apparent forage digestibility of dry matter,crude protein,and acid detergent fiber was significantly higher than that of O.aries.The 16s rRNA sequencing showed that the gut microbiota in WR underwent convergent evolution,and alpha diversity in these two groups was significantly higher than that in O.aries.Moreover,indicator species,including Bacteroidetes and Firmicutes,exhibited positive relationships with apparent forage digestibility,and their relative abundances were enriched in the gut of WR.Enterotype analysis further revealed that enterotype 1 belonged to WR,and the abundance of fatty acid synthesis metabolic pathway-related enzyme genes was significantly higher than enterotype 2,represented by O.aries.Besides,the metagenomic analysis identified 14 pathogenic bacterial species,among which 10 potentially pathogenic bacteria were significantly enriched in the gut microbiota of O.aries.Furthermore,the cellulolytic strains and genes encoding cellulase and hemicellulase were significantly enriched in WR.In conclusion,our results provide new evidence of gut microbiota to facilitate wildlife adaption in severe foraging environments of the TRSNP,China.
基金supported by the National Natural Science Foundation of China(32271226,31971097,32070751 and 31871435)the National Key Research and Development Program of China(2020YFA0803801)+1 种基金Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan(21XD1403200)the Key Laboratory of Exercise and Health Sciences(Shanghai University of Sport),Ministry of Education。
文摘Exercise is widely recognized for its extensive health benefits,ranging from cardiovascular protection to improved metabolic function and immune regulation.However,exercise-induced physiological adaptations are highly dependent on duration and frequency(Sanford et al.,2020).While acute exercise(AE)rapidly activates metabolic and immune responses(Mo Tr PAC Study Group et al.,2024),long-term exercise(LE)brings profound and systemic benefits,such as enhanced immunity,tissue regeneration,improved neuroplasticity,and cognitive function,optimized skeletal muscle metabolism and insulin sensitivity,and alleviation of chronic inflammation(De Miguel et al.,2021).
基金supported by Shanghai Oriental Talent Youth Program(QNKJ2024006)National Natural Science Foundation of China(82170555,32300523,32570769,and 62132015)+1 种基金Shanghai Academic/Technology Research Leader(22XD1422400)Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG06).
文摘Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies.By characterizing key molecular,cellular and niche events at the precancerous tipping point of early gastric cancer(EGC),we aimed to develop more precise screening tools and design targeted interventions to prevent malignant transformation at this stage.We utilized our AI models to integrate spatial multimodal data from nine EGC endoscopic submucosal dissection(ESD)samples(covering sequential stages from normal to cancer),construct a spatial-temporal profile of disease progression,and identify a critical tipping point(PMC_P)characterized by an immune-suppressive microenvironment during early cancer development.At this stage,inflammatory pit mucous cells with stemness(PMC_2)interact with fibroblasts via NAMPT→ITGA5/ITGB1 and with macrophages via AREG→EGFR/ERBB2 signaling,fostering cancer initiation.We established gastric precancerous cell lines and organoids to demonstrate that NAMPT and AREG promote cellular proliferation in vitro.Furthermore,in the transgenic CEA-SV40 mouse model,targeting AREG and/or NAMPT disrupted key cell interactions,inhibited the JAK-STAT,MAPK,and NFκB pathways,and reduced PD-L1 expression,which was also confirmed by western blot in vitro.These interventions delayed disease progression,reversed the immunosuppressive microenvironment,and prevented malignant transformation.Clinical validation was conducted using endoscopically resected EGC specimens.Our study provides a precise spatiotemporal depiction of EGC development and identifies novel diagnostic markers and therapeutic targets for early intervention.
基金supported by the Bio&Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science and ICT(2021R1A2C2094629 and 2017M3A9E9072669 to Hye Ryun Kim,and 2018R1A5A2025079,2022M3A9F3016364,and 2022R1A2C1092062 to Insuk Lee)supported in part by Brain Korea 21(BK21)FOUR program+1 种基金supported by the Technology Innovation Program(20022947)funded by the Ministry of Trade Industry&Energy(MOTIE,Korea)supported by the Yonsei Fellow Program,funded by Lee Youn Jae.
文摘Lung cancer remains the leading cause of cancer death in 2024,with∼80%being non-small cell lung cancer(NSCLC).Anaplastic lymphoma kinase(ALK)rearrangements occur in∼5%of NSCLC cases,typically treated with ALK inhibitors,though resistance often develops[1].Immunotherapy has been explored for advanced or resistant ALK-positive NSCLC,but immune checkpoint blockade(ICB)treatments have shown limited clinical benefits[1].
文摘Cancer is a complex and heterogeneous disease characterized by various genetic and epigenetic alterations.Early diagnosis,accurate subtyping,and staging are essential for effective,personalized treatment and improved survival rates.Traditional diagnostic methods,such as biopsies,are invasive and carry operational risks that hinder repeated use,underscoring the need for noninvasive and personalized alternatives.In response,this study integrates transcriptomic data into human genome-scale metabolic models(GSMMs)to derive patient-specific flux distributions,which are then combined with genomic,proteomic,and fluxomic(JX)data to develop a robust multi-omic classifier for lung cancer subtyping and early diagnosis.The JX classifier is further enhanced by analyzing heterogeneous datasets from RNA sequencing and microarray analyses derived from both tissue samples and cell culture experiments,thereby enabling the identification of key marker features and enriched pathways such as lipid metabolism and energy production.This integrated approach not only demonstrates high performance in distinguishing lung cancer subtypes and early-stage disease but also proves robust when applied to limited pancreatic cancer data.By linking genotype to phenotype,GSMM-driven flux analysis overcomes challenges related to metabolome data scarcity and platform variability by proposing marker processes and reactions for further investigation,ultimately facilitating noninvasive diagnostics and the identification of actionable biomarkers for targeted therapeutic intervention.These findings offer significant promise for streamlining clinical workflows and enabling personalized therapeutic strategies,and they highlight the potential of our versatile workflow for unveiling novel biomarker landscapes in less studied diseases.
基金supported by the National Natural Science Foundation of China(grant numbers:81902560,81730073).
文摘Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.
文摘The increasing integration of new technologies is driving a fundamental revolution in the healthcare sector.Developments in artificial intelligence(AI),machine learning,and big data analytics have completely transformed the diagnosis,treatment,and care of patients.AI-powered solutions are enhancing the efficiency and accuracy of healthcare delivery by demonstrating exceptional skills in personalized medicine,early disease detection,and predictive analytics.Furthermore,telemedicine and remote patient monitoring systems have overcome geographical constraints,offering easy and accessible healthcare services,particularly in underserved areas.Wearable technology,the Internet of Medical Things,and sensor technologies have empowered individuals to take an active role in tracking and managing their health.These devices facilitate real-time data collection,enabling preventive and personalized care.Additionally,the development of 3D printing technology has revolutionized the medical field by enabling the production of customized prosthetics,implants,and anatomical models,significantly impacting surgical planning and treatment strategies.Accepting these advancements holds the potential to create a more patient-centered,efficient healthcare system that emphasizes individualized care,preventive care,and better overall health outcomes.This review's novelty lies in exploring how these technologies are radically transforming the healthcare industry,paving the way for a more personalized and effective healthcare for all.It highlights the capacity of modern technology to revolutionize healthcare delivery by addressing long-standing challenges and improving health outcomes.Although the approval and use of digital technology and advanced data analysis face scientific and regulatory obstacles,they have the potential for transforming translational research.as these technologies continue to evolve,they are poised to significantly alter the healthcare environment,offering a more sustainable,efficient,and accessible healthcare ecosystem for future generations.Innovation across multiple fronts will shape the future of advanced healthcare technology,revolutionizing the provision of healthcare,enhancing patient outcomes,and equipping both patients and healthcare professionals with the tools to make better decisions and receive personalized treatment.As these technologies continue to develop and become integrated into standard healthcare practices,the future of healthcare will probably be more accessible,effective,and efficient than ever before.
基金supported by the“Centro de Investigacion Biomédica en Red Fisiopatología de la Obesidad y Nutricion”,which is an initiative of the“Instituto de Salud Carlos III”(ISCIII)of Spain,financed by the European Regional Development Fund under“A way to make Europe"/"Investing in your future”(CB06/03),a grant from ISCIII(No.PI18/01399,PI21/00633)UMA-FEDERJA-085,from Programa Operativo FEDER 2014–2020 of the Consejería de Economía y Conocimiento de la Junta de Andalucía+4 种基金a grant from the Consejeria Universidad,Investigacion e Innovacion Junta de Andalucia(No.PY20-01270,PI0293-2019)H.B.was supported by a predoctoral fellowship“Plan Propio IBIMA 2020 A.1 Contratos predoctorales”(No.predoc20_002)by a“Sara Borrell”postdoctoral contract(No.CD22/00053)from the Instituto de Salud Carlos III—Madrid(Spain),“Financiado por la Unión Europea—NextGenerationEU”,and the plan Recuperación,Transformación y Resiliencia.L.A.G.-F.was supported by a“Sara Borrell”postdoctoral contract(No.CD21/000131)from the Instituto de Salud Carlos III—Madrid(Spain)G.M.M.-N.was supported by a postdoctoral contract from the University of Malaga(No.UMA20-FEDERJA-092)M.M.G.was the recipient of the Nicolas Monardes Programme from the“Servicio Andaluz de Salud,Junta de Andalucia”,Spain(No.RC-0001-2018,C-0029-2014).
文摘Colorectal cancer(CRC)continues to be the third most frequently diagnosed cancer,and the second leading cause of cancer-related mortality.Several non-invasive biomarkers have emerged,but only a few have been incorporated into clinical practice due to the lack of sensitivity.1 Research on the epigenome has unveiled potential clinical applications for diagnosis and therapy response.2,3 Particularly,recent evidence suggests a novel role of RNA methylation in the development of CRC,4 revealing an overall RNA m6A hypomethylation.5 However,our understanding of their contribution to CRC remains limited.
