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Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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中华医学杂志(英文版) 2024年第7期137卷 859-870页

作者： Wang Xianlong Zhao Chuan Lin Jincheng Liu Hongxing Zeng Qiuhong Chen Huadong Wang Ye Xu Dapeng Chen Wen Xu Moping Zhang En Lin Da Lin Zhixiong Sanbo Brain Hospital Capital Medical University Beijing 100093 Department of bioinformatics School of Medical Technology and Engineering Key laboratory of Medical bioinformatics Key laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical University Fuzhou Fujian 350122 China Department of Neurosurgery

Background: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox,P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB (P = 0.01).Conclusions: ACP comprises three molecular subtypes with disti

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

Complicated evolutionary patterns of microRNAs in vertebrates

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Science China(Life Sciences) 2008年第6期51卷 552-559页

作者： WANG XiaoWo, ZHANG XueGong & LI YanDa MOE Key laboratory of bioinformatics and bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China MOE Key laboratory of bioinformatics and bioinformatics Division TNLIST / Department of Automation Tsinghua University Beijing China

MicroRNAs (miRNAs) are a class of ～22 nt long endogenous non-coding RNAs that play important regulatory roles in diverse organisms. Up to now, little is known about the evolutionary properties of these crucial regulators. Most miRNAs were thought to be phylogenetically conserved, but recently, a number of poorly-conserved miRNAs have been reported and miRNA innovation is shown to be an ongoing process. In this work, through the characterization of an miRNA super family, we studied the evolutionary patterns of miRNAs in vertebrates. Recently generated miRNAs seem to evolve rapidly during a certain period following their emergence. Multiple lineage-specific expansions were observed. Homolgous premiRNAs may produce mature products from the opposite stem arms following tandem duplications, which may have important contribution to miRNA innovation. Our observations of miRNAs' complicated evolutionary patterns support the notion that these key regulatory molecules may play very active roles in evolution.

关键词： microRNA evolution miRNA:miRNA* interconversion lineage specific duplication

Comparative Study of Apoptosis-related Gene Loci in Human,Mouse and Rat Genomes

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Acta Biochimica et Biophysica Sinica 2005年第5期37卷 341-348页

作者： Yan-Bin YIN Yong ZHANG Peng YU Jing-Chu LUO Ying JIANG Song-Gang LI Center of bioinformatics, National laboratory. of Genetic Engineering and Protein Engineering, College of Life Sciences Peking University,Beijing 100871, China Center of bioinformatics National Laboratory of Genetic Engineering and Protein Engineering College of Life Sciences Peking UniversityBeijing 100871 China

Many genes are involved in mammalian cell apoptosis pathway.These apoptosis genes oftencontain characteristic functional domains,and can be classified into at least 15 functional groups,accordingto previous reports.Using an integrated bioinformatics platform for motif or domain search from threepublic mammalian proteomes(International Protein Index database for human,mouse,and rat),we system-atically cataloged all of the proteins involved in mammalian apoptosis pathway.By localizing those proteinsonto the genomes,we obtained a gene locus centric apoptosis gene catalog for human,mouse and rat.Further phylogenetic analysis showed that most of the apoptosis related gene loci are conserved amongthese three mammals.Interestingly,about one-third of apoptosis gene loci form gene clusters on mammalchromosomes,and exist in the three species,which indicated that mammalian apoptosis gene orders arealso conserved.In addition,some tandem duplicated gene loci were revealed by comparing gene loci clustersin the three species.All data produced in this work were stored in a relational database and may be viewedat http://***/database/apd.php.

关键词： apoptosis gene cluster comparative genomics bioinformatics

Curation,nomenclature,and topological classification of receptor-like kinases from 528 plant species for novel domain discovery and functional inference

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Molecular Plant 2024年第4期17卷 658-671页

作者： Qian Liu Qiong Fu Yujie Yan Qian Jiang Longfei Mao Long Wang Feng Yu Heping Zheng State Key laboratory of Chemo/Biosensing and Chemometrics Hunan University College of BiologyChangshaHunan 410082China bioinformatics Center Hunan University College of BiologyChangshaHunan 410082China

Receptor-like kinases(RLKs)are the most numerous signal transduction components in plants and play important roles in determining how different plants adapt to their ecological environments.Research on RLKs has focused mainly on a small number of typical RLK members in a few model plants.There is an urgent need to study the composition,distribution,and evolution of RLKs at the holistic level to increase our understanding of how RLKs assist in the ecological adaptations of different plant species.In this study,we collected the genome assemblies of 528 plant species and constructed an RLK dataset.Using this dataset,we identified and characterized 524948 RLK family members.Each member underwent systematic topological classification and was assigned a gene ID based on a unified nomenclature system.Furthermore,we identified two novel extracellular domains in some RLKs,designated Xiao and Xiang.Evolutionary analysis of the RLK family revealed that the RLCK-XVII and RLCK-XII-2 classes were present exclusively in dicots,suggesting that diversification of RLKs between monocots and dicots may have led to differences in downstream cytoplasmic responses.We also used an interaction proteome to help empower data mining for inference of new RLK functions from a global perspective,with the ultimate goal of understanding how RLKs shape the adaptation of different plants to the environments/ecosystems.The assembled RLK dataset,together with annotations and analytical tools,forms an integrated foundation of multiomics data that is publicly accessible via the metaRLK web portal(http://metaRLK.biocloud.top).

关键词： RLK RLCK domain signaling pathway receptor-protein interactions

Interplant communication:an emerging battlefield in plant-aphid-virus interactions

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Science China(Life Sciences) 2024年第5期67卷 1069-1071页

作者： Yunjing Wang Qian Gong Yule Liu MOE Key laboratory of bioinformatics and Center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Beijing 100084China

Plants constantly face threats from various organisms,including pathogens and herbivores.Among the pathogens,plant viruses are obligate intracellular parasites that infect plants and cause serious crop yield losses.

关键词： plant Plants communication

Crystal Structure of the MH2 domain of Drosophila Mad

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Science China(Life Sciences) 2009年第6期52卷 539-544页

作者： WANG Chong,CHEN Lei,WANG Le & WU JiaWei MOE Key laboratory of bioinformatics,Department of Biological Sciences and Biotechnology,Tsinghua University,Beijing 100084,China MOE Key laboratory of bioinformatics Department of Biological Sciences and Biotechnology Tsinghua University Beijing China

The decapentaplegic(Dpp),a member of the TGF-β superfamily,plays a pivotal role in the control of proliferation,global patterning and induction of specific cell fates during Drosophila development.Mother against Dpp(Mad) is the founding member of the conserved Smad protein family which spe-cifically transduces the intracellular TGF-β signaling cascade.Here we report the 2.80 structure of the MH2 domain of Mad(Mad-MH2) that was readily superposed to the mammal Smad-MH2 structures.This unphosphorylated Mad-MH2 forms a symmetric homotrimer in crystals,consistent with the result of the size-exclusion chromatography that Mad-MH2 exhibited a propensity for concentration-dependent oligomerization prior to phosphorylation.Structural analysis revealed that the formation of homotrimeric Mad-MH2 is mainly mediated by contacts involving the extreme C-terminal SSVS motif,and is strengthened by phosphorylation of the last two Ser residues which was confirmed by the gel filtration analysis of the pseudophosphorylated Mad-MH2(DVD).Intriguingly,the homotrimer within an asymmetric unit only possesses two ordered C-terminal tails,reminiscent of the arrangement of the R-Smad/Smad4 complexes,indicating that the subunit with a flexible SSXS motif would be readily replaced by Co-Smad to form a functional heterotrimer.

关键词： TGF-β signaling Smad protein family MH2 domain crystal structure homotrimerization

An overview of detecting gene-trait associations by integrating GWAS summary statistics and eQTLs

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Science China(Life Sciences) 2024年第6期67卷 1133-1154页

作者： Yang Zhang Mengyao Wang Zhenguo Li Xuan Yang Keqin Li Ao Xie Fang Dong Shihan Wang Jianbing Yan Jianxiao Liu National Key laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan 430070China Key laboratory of Smart Farming for Agricultural Animals Huazhong Agricultural UniversityWuhan 430070China Hubei Key laboratory of Agricultural bioinformatics Huazhong Agricultural UniversityWuhan 430070China College of Informatics Huazhong Agricultural UniversityWuhan 430070China College of Life Sciences Nankai UniversityTianjin 300071China

Detecting genes that affect specific traits(such as human diseases and crop yields)is important for treating complex diseases and improving crop quality.A genome-wide association study(GWAS)provides new insights and directions for understanding complex traits by identifying important single nucleotide polymorphisms.Many GWAS summary statistics data related to various complex traits have been gathered recently.Studies have shown that GWAS risk loci and expression quantitative trait loci(e QTLs)often have a lot of overlaps,which makes gene expression gradually become an important intermediary to reveal the regulatory role of GWAS.In this review,we review three types of gene-trait association detection methods of integrating GWAS summary statistics and e QTLs data,namely colocalization methods,transcriptome-wide association study-oriented approaches,and Mendelian randomization-related methods.At the theoretical level,we discussed the differences,relationships,advantages,and disadvantages of various algorithms in the three kinds of gene-trait association detection methods.To further discuss the performance of various methods,we summarize the significant gene sets that influence highdensity lipoprotein,low-density lipoprotein,total cholesterol,and triglyceride reported in 16 studies.We discuss the performance of various algorithms using the datasets of the four lipid traits.The advantages and limitations of various algorithms are analyzed based on experimental results,and we suggest directions for follow-up studies on detecting gene-trait associations.

关键词： gene-trait association GWAS eQTL colocalization transcriptome-wide association study(TWAS) Mendelian randomization(MR)

Perspective on new cell-free DNA technologies for early cancer detection

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Cancer Biology & Medicine 2024年第2期21卷 139-143页

作者： Jie Li Xun Lan Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing 100084China MOE Key laboratory of bioinformatics Tsinghua UniversityBeijing 100084China Tsinghua-Peking Joint Center for Life Sciences Tsinghua UniversityBeijing 100084China

High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients with early-stage cancer after standard treatment.Although traditional cancer detection technologies,such as endoscopy for gastrointestinal cancer,mammography for breast cancer。

关键词： prognosis cancer patients

scEpiTools: a database to comprehensively interrogate analytic tools for single-cell epigenomic data

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Journal of Genetics and Genomics 2024年第4期51卷 462-465页

作者： Zijing Gao Xiaoyang Chen Zhen Li Xuejian Cui Qun Jiang Keyi Li Shengquan Chen Rui Jiang Ministry of Education Key laboratory of bioinformatics Bioinformatics Division at the Beijing National Research Center for Information Science and TechnologyCenter for Synthetic and Systems BiologyDepartment of AutomationTsinghua UniversityBeijing 100084China School of Mathematical Sciences and LPMC Nankai UniversityTianjin 300071China

Recent advances in single-cell sequencing technologies provide significant implications for understanding cellular heterogeneity,developmental biology,and disease mechanisms.To fully exploit the potential of these data,numerous tools have been proposed for upstream and downstream analyses.In the the single-cell RNA sequencing(scRNA-seq)community,scRNA-tools(Zappia et al.,2018)was proposed to help researchers navigate the plethora of tools by category.Since its inception,scRNA-tools has been widely used and its updated version further reveals trends in the field with over 1000 collected tools(Zappia and Theis,2021),providing a valuable guidance in selecting tools for analyses.

关键词： analytic selecting Tools