Tumor bioinformatics plays an important role in cancer research and precision medicine.The primary focus of traditional cancer research has been molecular and clinical studies of a number of fundamental pathways and g...Tumor bioinformatics plays an important role in cancer research and precision medicine.The primary focus of traditional cancer research has been molecular and clinical studies of a number of fundamental pathways and genes.In recent years,driven by breakthroughs in high-throughput technologies,large-scale cancer omics data have accumulated rapidly.How to effectively utilize and share these data is particularly important.To address this crucial task,many computational tools and databases have been developed over the past few years.To help researchers quickly learn and understand the functions of these tools,in this review,we summarize publicly available bioinformatics tools and resources for pan-cancer multi-omics analysis,regulatory analysis of tumorigenesis,tumor treatment and prognosis,immune infiltration analysis,immune repertoire analysis,cancer driver gene and driver mutation analysis,and cancer single-cell analysis,which may further help researchers find more suitable tools for their research.展开更多
Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection...Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection.This intercontinental,hospital-based,diagnostic study included 761 treatment-naive inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers(China,n=3;Netherlands,n=5;Poland,n=1)between September 2016 and May 2019.The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese(VC1 and VC2)and the European(VC3)validation cohorts collectively and independently.Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets.The AUCs for TEPs in the combined validation cohort,VC1,VC2,and VC3 were 0.918(95%CI 0.889-0.948),0.923(0.855-0.990),0.918(0.872-0.963),and 0.887(0.813-0.960),respectively.Combination of TEPs and CA125 demonstrated an AUC of 0.922(0.889-0.955)in the combined validation cohort;0.955(0.912-0.997)in VC1;0.939(0.901-0.977)in VC2;0.917(0.824-1.000)in VC3.For subgroup analysis,TEPs exhibited an AUC of o.858,0.859,and 0.920 to detect early-stage,borderline,non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis.TEPs had robustness,compatibility,and universality for preop.erative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities,heterogeneous histoiogical subtypes,and early-stage ovarian cancer.However,these observations warrant prospective validations in a larger population beforeclinicalutilities.展开更多
Dear Editor,Platelets are circulating anucleate cytoplasmic fragments of megakaryocytes and characterized by their functions in wound healing and vascular integrity maintenance.Increasing evidence highlights the exten...Dear Editor,Platelets are circulating anucleate cytoplasmic fragments of megakaryocytes and characterized by their functions in wound healing and vascular integrity maintenance.Increasing evidence highlights the extensive reciprocal signaling interactions between platelets and tumor cells(Haemmerle et al.,2018).Tumor cells activate and aggregate platelets to sustain proliferation(Cho et al.,2012),resist apoptosis,and promote metastasis(Haemmerle et al.,2017).展开更多
Transcription factors(TFs)as key regulators play crucial roles in biological processes.The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gen...Transcription factors(TFs)as key regulators play crucial roles in biological processes.The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression.The accumulated data of chromatin immunoprecipitation sequencing(ChIP-seq)provide great opportunities to discover the TF-target regulations across different conditions.In this study,we constructed a database named hTFtarget,which integrated huge human TF target resources(7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs)and epigenetic modification information to predict accurate TF-target regulations.hTFtarget offers the following functions for users to explore TF-target regulations:(1)browse or search general targets of a query TF across datasets;(2)browse TF-target regulations for a query TF in a specific dataset or tissue;(3)search potential TFs for a given target gene or noncoding RNA;(4)investigate co-association between TFs in cell lines;(5)explore potential coregulations for given target genes or TFs;(6)predict candidate TF binding sites on given DNA sequences;(7)visualize ChIP-seq peaks for different TFs and conditions in a genome browser.hTFtarget provides a comprehensive,reliable and user-friendly resource for exploring human TF-target regulations,which will be very useful for a wide range of users in the TF and gene expression regulatiol community.hTFtarget is available at bttp://bioinfo.life.hust.edu.cn/hTFtarget.展开更多
Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblast...Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells,and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations,e.g.,CD8+T cells and natural killer (NK) cells,in the bone marrow. Additionally,CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways,including the NK cell mediated cytotoxicity and NOD-like recep-tor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g.,miR-148a-3p and miR-375),acting as oncogenes or tumor suppressors,could regulate the crosstalk between the genes encoding transcription factors (TFs,e.g.,JUN and FOS) and histones (e.g.,HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore,many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g.,FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for fur-ther understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.展开更多
Non-coding regions are the major component of human genomes and the long non-coding RNA（IncRNA）is a class of pervasive genes located in noncoding regions（Morris and Mattick,2014）.IncRNAs play a wide range of regul...Non-coding regions are the major component of human genomes and the long non-coding RNA（IncRNA）is a class of pervasive genes located in noncoding regions（Morris and Mattick,2014）.IncRNAs play a wide range of regulatory roles in gene transcription,translation,epigenetic modification and protein function by interacting with different types of molecules including DNA,展开更多
基金supported by a grant of the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYYC23007).
文摘Tumor bioinformatics plays an important role in cancer research and precision medicine.The primary focus of traditional cancer research has been molecular and clinical studies of a number of fundamental pathways and genes.In recent years,driven by breakthroughs in high-throughput technologies,large-scale cancer omics data have accumulated rapidly.How to effectively utilize and share these data is particularly important.To address this crucial task,many computational tools and databases have been developed over the past few years.To help researchers quickly learn and understand the functions of these tools,in this review,we summarize publicly available bioinformatics tools and resources for pan-cancer multi-omics analysis,regulatory analysis of tumorigenesis,tumor treatment and prognosis,immune infiltration analysis,immune repertoire analysis,cancer driver gene and driver mutation analysis,and cancer single-cell analysis,which may further help researchers find more suitable tools for their research.
文摘Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection.This intercontinental,hospital-based,diagnostic study included 761 treatment-naive inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers(China,n=3;Netherlands,n=5;Poland,n=1)between September 2016 and May 2019.The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese(VC1 and VC2)and the European(VC3)validation cohorts collectively and independently.Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets.The AUCs for TEPs in the combined validation cohort,VC1,VC2,and VC3 were 0.918(95%CI 0.889-0.948),0.923(0.855-0.990),0.918(0.872-0.963),and 0.887(0.813-0.960),respectively.Combination of TEPs and CA125 demonstrated an AUC of 0.922(0.889-0.955)in the combined validation cohort;0.955(0.912-0.997)in VC1;0.939(0.901-0.977)in VC2;0.917(0.824-1.000)in VC3.For subgroup analysis,TEPs exhibited an AUC of o.858,0.859,and 0.920 to detect early-stage,borderline,non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis.TEPs had robustness,compatibility,and universality for preop.erative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities,heterogeneous histoiogical subtypes,and early-stage ovarian cancer.However,these observations warrant prospective validations in a larger population beforeclinicalutilities.
基金supported by the National Science and Technology Major Sub-Project (2018ZX10301402-002)National Natural Science Foundation of China (81772787,82072889,31822030,and 31771458)+2 种基金Technical Innovation Special Project of Hubei Province (2018ACA138)Fundamental Research Funds for the Central Universities (2019kfyXMBZ024)Wuhan Municipal Health Commission (WX18Q16).
文摘Dear Editor,Platelets are circulating anucleate cytoplasmic fragments of megakaryocytes and characterized by their functions in wound healing and vascular integrity maintenance.Increasing evidence highlights the extensive reciprocal signaling interactions between platelets and tumor cells(Haemmerle et al.,2018).Tumor cells activate and aggregate platelets to sustain proliferation(Cho et al.,2012),resist apoptosis,and promote metastasis(Haemmerle et al.,2017).
基金funding from the National Natural Science Foundation of China(Grant Nos.31822030,31801113,and 31771458)National Key R&D Program of China(Grant No.2017YFA0700403)China Postdoctoral Science Foundation(Grant No.2018M632830)
文摘Transcription factors(TFs)as key regulators play crucial roles in biological processes.The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression.The accumulated data of chromatin immunoprecipitation sequencing(ChIP-seq)provide great opportunities to discover the TF-target regulations across different conditions.In this study,we constructed a database named hTFtarget,which integrated huge human TF target resources(7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs)and epigenetic modification information to predict accurate TF-target regulations.hTFtarget offers the following functions for users to explore TF-target regulations:(1)browse or search general targets of a query TF across datasets;(2)browse TF-target regulations for a query TF in a specific dataset or tissue;(3)search potential TFs for a given target gene or noncoding RNA;(4)investigate co-association between TFs in cell lines;(5)explore potential coregulations for given target genes or TFs;(6)predict candidate TF binding sites on given DNA sequences;(7)visualize ChIP-seq peaks for different TFs and conditions in a genome browser.hTFtarget provides a comprehensive,reliable and user-friendly resource for exploring human TF-target regulations,which will be very useful for a wide range of users in the TF and gene expression regulatiol community.hTFtarget is available at bttp://bioinfo.life.hust.edu.cn/hTFtarget.
基金the National Natural Science Foundation of China (Grant Nos. 31822030, 31801113, and 31771458)the National Key R&D Program of China (Grant No. 2017YFA0700403)China Postdoctoral Science Foundation (Grant No. 2018M632830)
文摘Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells,and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations,e.g.,CD8+T cells and natural killer (NK) cells,in the bone marrow. Additionally,CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways,including the NK cell mediated cytotoxicity and NOD-like recep-tor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g.,miR-148a-3p and miR-375),acting as oncogenes or tumor suppressors,could regulate the crosstalk between the genes encoding transcription factors (TFs,e.g.,JUN and FOS) and histones (e.g.,HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore,many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g.,FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for fur-ther understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
基金supported by the National Natural Science Foundation of China(Nos.31270885 and 31471247)the open fund of Functional Oil Laboratory Associated by Oil Crops Research Institute,Chinese Academy of Agricultural Sciences and Infinitus (China) Company Ltd
文摘Non-coding regions are the major component of human genomes and the long non-coding RNA（IncRNA）is a class of pervasive genes located in noncoding regions（Morris and Mattick,2014）.IncRNAs play a wide range of regulatory roles in gene transcription,translation,epigenetic modification and protein function by interacting with different types of molecules including DNA,
