The genetic variation in Northern Asian populations is currently undersampled. To address this, we generated a new genetic variation reference panel by whole-genome sequencing of 175 ethnic Mongolians, representing six tribes. The cataloged variation in the panel shows strong population stratification among these tribes, which correlates with the diverse demographic histories in the region. Incorporating our results with the 1000 Genomes Project panel identifies derived alleles shared between Finns and Mongolians/Siberians, suggesting that substantial gene flow between northern Eurasian populations has occurred in the past. Furthermore, we highlight that North, East, and Southeast Asian populations are more aligned with each other than these groups are with South Asian and Oceanian populations.

Haihua Bai;Xiaosen Guo;Narisu Narisu;Tianming Lan;Qizhu Wu;Yanping Xing;Yong Zhang;Stephen R. Bond;Zhili Pei;Yanru Zhang;Dandan Zhang;Jirimutu Jirimutu;Dong Zhang;Xukui Yang;Morigenbatu Morigenbatu;Li Zhang;Bingyi Ding;Baozhu Guan;Junwei Cao;Haorong Lu;Yiyi Liu;Wangsheng Li;Ningxin Dang;Mingyang Jiang;Shenyuan Wang;Huixin Xu;Dingzhu Wang;Chunxia Liu;Xin Luo;Ying Gao;Xueqiong Li;Zongze Wu;Liqing Yang;Fanhua Meng;Xiaolian Ning;Hashenqimuge Hashenqimuge;Kaifeng Wu;Bo Wang;Suyalatu Suyalatu;Yingchun Liu;Chen Ye;Huiguang Wu;Kalle Leppälä;Lu Li;Lin Fang;Yujie Chen;Wenhao Xu;Tao Li;Xin Liu;Xun Xu;Christopher R. Gignoux;焕明 杨;Lawrence C. Brody;军 王;Karsten Kristiansen;Burenbatu Burenbatu;Huanmin Zhou;Ye Yin

Nature Genetics

2018-12-1

Mounting evidence suggests that terrestrialization of plants started in streptophyte green algae, favoured by their dual existence in freshwater and subaerial/terrestrial environments. Here, we present the genomes of Mesostigma viride and Chlorokybus atmophyticus, two sister taxa in the earliest-diverging clade of streptophyte algae dwelling in freshwater and subaerial/terrestrial environments, respectively. We provide evidence that the common ancestor of M. viride and C. atmophyticus (and thus of streptophytes) had already developed traits associated with a subaerial/terrestrial environment, such as embryophyte-type photorespiration, canonical plant phytochrome, several phytohormones and transcription factors involved in responses to environmental stresses, and evolution of cellulose synthase and cellulose synthase-like genes characteristic of embryophytes. Both genomes differed markedly in genome size and structure, and in gene family composition, revealing their dynamic nature, presumably in response to adaptations to their contrasting environments. The ancestor of M. viride possibly lost several genomic traits associated with a subaerial/terrestrial environment following transition to a freshwater habitat.

Sibo Wang;Linzhou Li;Haoyuan Li;Sunil Kumar Sahu;Hongli Wang;Yan Xu;Wenfei Xian;Bo Song;Hongping Liang;Shifeng Cheng;Yue Chang;Yue Song;Zehra Çebi;Sebastian Wittek;Tanja Reder;Morten Peterson;焕明 杨;Jian Wang;Barbara Melkonian;Yves Van de Peer;Xun Xu;Gane Ka Shu Wong;Michael Melkonian;Huan Liu;Xin Liu

Nature Plants

2020-2-1

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

Feng Zhu;Yanmei Ju;Wei Wang;Qi Wang;Ruijin Guo;Qingyan Ma;Qiang Sun;Yajuan Fan;Yuying Xie;Zai Yang;Zhuye Jie;Binbin Zhao;Liang Xiao;Lin Yang;Tao Zhang;Junqin Feng;Liyang Guo;Xiaoyan He;Yunchun Chen;Ce Chen;Chengge Gao;Xun Xu;焕明 杨;Jian Wang;Yonghui Dang;Lise Madsen;Susanne Brix;Karsten Kristiansen;Huijue Jia;Xiancang Ma

Nature Communications

2020-12-1

Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM:*606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

Peter Bross;Zhijie Li;Jakob Hansen;Jens Jacob Hansen;Marit Nyholm Nielsen;Thomas Juhl Corydon;Costa Georgopoulos;Debbie Ang;Jytte Banner Lundemose;Klary Niezen-Koning;Hans Eiberg;焕明 杨;Steen Kølvraa;Lars Bolund;Niels Gregersen

Journal of Human Genetics

2007-1

Background: The rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen. Results: Using deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig, and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e., 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes, which explains the great adaptability of cattle to rapidly adjust to dietary changes. Conclusions: These data bring new insights into functions, carbohydrate-degrading enzymes, and microbes of the rumen to complement the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data are made available.

Junhua Li;Huanzi Zhong;Yuliaxis Ramayo-Caldas;Nicolas Terrapon;Vincent Lombard;Gabrielle Potocki-Veronese;Jordi Estellé;Milka Popova;Ziyi Yang;Hui Zhang;Fang Li;Shanmei Tang;Fangming Yang;Weineng Chen;Bing Chen;Jiyang Li;Jing Guo;Cécile Martin;Emmanuelle Maguin;Xun Xu;焕明 杨;Jian Wang;Lise Madsen;Karsten Kristiansen;Bernard Henrissat;Stanislav D. Ehrlich;Diego P. Morgavi

GigaScience

2020-6-10

焕明 杨

Ukrainian Biochemical Journal

2013

Metaproteomics is a new frontier of microbiological science that collects the proteomic data from microbes in nature using mass spectrometry and explores the corresponding genetic and biochemical mechanisms with systematical bioinformatics. In contrast to the traditional approach, metaproteomic informatics adopts new strategies, including algorithms, databases and searches. As the metaproteomic samples generally contain very complicated protein components, a large dataset with all the potential microbe genomes is basically required for searching peptides based on the signals of mass spectrometry, while such searching process is real time-consuming. Several considerable factors such as dataset capacity, searching strategy and false positive control, therefore, have to be carefully evaluated to achieve the better results of protein identification with an acceptable accuracy and efficiency. Meanwhile, except a common sequence merger in proteomic informatics, metaproteomics has to deal with the issues of vast sequence homologous and species grouping. Solving these problems relies on effective utilization to the public information gained from NCBI for species classification, and filtration treatment from sequence to species using LCA algorithm. Herein, we briefly introduce this field, including which is the basic informatics strategy of metaproteomics, what are the tough challenges in metaproteomic informatics, and how the technique difficulties are being solved in future.

Hong Kai Xu;Ke Qiang Yan;Yan Bin He;Bo Wen;焕明 杨;Si Qi Liu

Progress in Biochemistry and Biophysics

2018

While we celebrate the 20th anniversary of the complete decoding of the genetic code, we should also commemorate Prof. Brian Clark for his remarkable contributions to this historic landmark in life sciences, as well as to the global collaboration on sciences. As an international citizen and a great scientist, Prof. Brian Clark will live for ever in the hearts of all his friends and students.

焕明 杨

New Biotechnology

2017-9-25

Background: The human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing, the golden standard technology for HLA typing enables accurate identification of HLA alleles in high-resolution. However, only the commercial software, such as uTYPE, SBT-Assign, and SBTEngine, and very few open-source tools could be applied to perform HLA typing based on Sanger sequencing. Results: We developed a user-friendly, cross-platform and open-source desktop application, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles. SOAPTyping can produce accurate results with a comprehensible protocol and featured functions. Moreover, SOAPTyping supports a more advanced group-specific sequencing primers (GSSP) module to solve the ambiguous typing results. We used SOAPTyping to analyze 36 samples with known HLA typing from the University of California Los Angeles (UCLA) International HLA DNA Exchange platform and 100 anonymous clinical samples, and the HLA typing results from SOAPTyping are identical to the golden results and 5.5 times faster than commercial software uTYPE, which shows the usability of SOAPTyping. Conclusions: We introduce the SOAPTyping as the first open-source and cross-platform HLA typing software with the capability of producing high-resolution HLA typing predictions from Sanger sequence data.

Yong Zhang;Yongsheng Chen;Huixin Xu;Junbin Fang;Zijian Zhao;Weipeng Hu;Xiaoqin Yang;Jia Ye;Yun Cheng;Jiayin Wang;Weiqiang Sun;Jian Wang;焕明 杨;Jing Yan;Lin Fang

BMC Bioinformatics

2020-7-8

Modeling of genomic profiles from the Cancer Genome Atlas (TCGA) by using recently developed mathematical frameworks has associated a genome-wide pattern of DNA copy-number alterations with a shorter, roughly one-year, median survival time in glioblastoma (GBM) patients. Here, to experimentally test this relationship, we whole-genome sequenced DNA from tumor samples of patients. We show that the patients represent the U.S. adult GBM population in terms of most normal and disease phenotypes. Intratumor heterogeneity affects ≈ 11 % and profiling technology and reference human genome specifics affect <1% of the classifications of the tumors by the pattern, where experimental batch effects normally reduce the reproducibility, i.e., precision, of classifications based upon between one to a few hundred genomic loci by >30%. With a 2.25-year Kaplan-Meier median survival difference, a 3.5 univariate Cox hazard ratio, and a 0.78 concordance index, i.e., accuracy, the pattern predicts survival better than and independent of age at diagnosis, which has been the best indicator since 1950. The prognostic classification by the pattern may, therefore, help to manage GBM pseudoprogression. The diagnostic classification may help drugs progress to regulatory approval. The therapeutic predictions, of previously unrecognized targets that are correlated with survival, may lead to new drugs. Other methods missed this relationship in the roughly 3B-nucleotide genomes of the small, order of magnitude of 100, patient cohorts, e.g., from TCGA. Previous attempts to associate GBM genotypes with patient phenotypes were unsuccessful. This is a proof of principle that the frameworks are uniquely suitable for discovering clinically actionable genotype-phenotype relationships.

Sri Priya Ponnapalli;Matthew W. Bradley;Karen Devine;Jay Bowen;Sara E. Coppens;Kristen M. Leraas;Brett A. Milash;Fuqiang Li;Huijuan Luo;Shi Qiu;Kui Wu;焕明 杨;Carl T. Wittwer;Cheryl A. Palmer;Randy L. Jensen;Julie M. Gastier-Foster;Heidi A. Hanson;Jill S. Barnholtz-Sloan;Orly Alter

APL Bioengineering

2020-6-1