hTFtarget:A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets

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.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.