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Journal of Genetics and Genomics 2015年第8期42卷 445-453页

作者： Jiawei Shen Zhiqiang Li yongyong shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) Shanghai Jiao Tong University Institute of Social Cognitive and Behavioral Sciences Shanghai Jiao Tong University School of Bio-medical Engineering Shanghai Jiao Tong University Shanghai Changning Mental Health Center

Population stratification is a problem in genetic association studies because it is likely to highlight loci that underlie the population structure rather than disease-related loci. At present, principal component analysis （PCA） has been proven to be an effective way to correct for population stratification. However, the conventional PCA algorithm is time-consuming when dealing with large datasets. We developed a Graphic processing unit （GPU）-based PCA software named SHEsisPCA （http：//***/***） that is highly parallel with a highest speedup greater than 100 compared with its CPU version. A cluster algorithm based on X-means was also implemented as a way to detect population subgroups and to obtain matched cases and controls in order to reduce the genomic inflation and increase the power. A study of both simulated and real datasets showed that SHEsisPCA ran at an extremely high speed while the accuracy was hardly reduced. Therefore, SHEsisPCA can help correct for population stratification much more efficiently than the conventional CPU-based algorithms.

关键词： Population stratification Principal component analysis Graphic processing unit Cluster Matched cases and controls Genetic studies

Biological data processing based on bio-processor unit(BPU), a new concept for next generation computational biology

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Science China(Life Sciences) 2018年第5期61卷 597-598页

作者： Di Liu Dongbo Bu Tieliu shi Jianxiao Quan Depeng Wang yongyong shi Xiao-Chen Bo Wenbao Han Computational Virology Group Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Key Laboratory of InteUigent Information Processing Institute of Computing Technology Chinese Academy of Sciences Beijing 100190 China Center for Bioinformatics and Computational Biology and the Institute of Biomedical Sciences School of Life Sciences East China Normal University Shanghai 200214 China State Key Laboratory of Mathematical Engineering and Advanced Computation Wuxi 214122 China Jiangsu Variable Supercomputer Tech Co Ltd. Wuxi 214125 China NextOmics Blosctences Wuhan 430074 China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) Shanghai Jiao Tong University Shanghai 200030 China Beijing Institute of Radiation Medicine Beifing 100850 China

The revolution of biotechnology has pushed forward life sciences into the Big Data ***,high-throughput bio-techniques have greatly accelerated the integration of biology,computing and informatics,and hence substantially pushed forward the development of bioinformatics and computational *** to the latest report of data deposition within National Centre for Biotechnology Information（NCBI）,the genome sequencing projects have increased 49.94%.

关键词：计算生物学简历处理器数据基信息科学生物信息学生命科学 NCBI

Decoding psychosis:from national genome project to national brain project

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General Psychiatry 2022年第4期35卷 214-223页

作者： Liya Sun Manfei Xu yongyong shi Yifeng Xu Jinghong Chen Lin He Shanghai Mental Health Center Editorial Office Shanghai Jiao Tong University School of MedicineShanghaiChina Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CentreShanghai Jiao Tong University School of MedicineShanghaiChina

The mind has puzzled humans for centuries,and its disorders,such as psychoses,have caused tremendous ***,relatively recent biotechnological breakthroughs,such as DNA technology and neuroimaging,have empowered scientists to explore the more fundamental aspects of *** searching for psychosis-causing genes to imaging the depths of the brain,scientists worldwide seek novel methods to understand the mind and the causes of its *** article will briefly review the history of understanding and managing psychosis and the main findings of modern genetic research and then attempt to stimulate thought for decoding the biological mechanisms of psychosis in the present era of brain science.

关键词： breakthrough sis psycho

Structural Analysis of the SARS-CoV-2 Omicron Variant Proteins

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Research 2021年第2期2021卷 759-762页

作者： Qiangzhen Yang Ali Alamdar Shah Syed Aamir Fahira yongyong shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong University1954 Huashan RoadShanghai 200030China Biomedical Sciences Institute of Qingdao University(Qingdao Branch of SJTU Bio-X Institutes) Qingdao UniversityQingdao 266003China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052China Department of Psychiatry First Teaching Hospital of Xinjiang Medical UniversityUrumqi830046China

The spread of the latest SARS-CoV-2 variant Omicron is particularly concerning because of the large number of mutations present in its genome and lack of knowledge about how these mutations would affect the current SARS-CoV-2 vaccines and ***,by performing phylogenetic analysis using the Omicron spike(S)protein sequence,we found that the Omicron S protein presented the longest evolutionary distance in relation to the other SARS-CoV-2 *** predicted the structures of S,M,and N proteins of the Omicron variant using AlphaFold2 and investigated how the mutations have affected the S protein and its parts,S1 NTD and RBD,in *** found many amino acids on RBD were mutated,which may influence the interactions between the RBD and ACE2,while also showing the S309 antibody could still be capable of neutralizing Omicron *** Omicron S1 NTD structures display significant differences from the original strain,which could lead to reduced recognition by antibodies resulting in potential immune escape and decreased effectiveness of the existing ***,this study of the Omicron variant was mainly limited to structural predictions,and these findings should be explored and verified by subsequent *** study provided basic data of the Omicron protein structures that lay the groundwork for future studies related to the SARS-CoV-2 Omicron variant.

关键词： concerning subsequent neutral

Structural Comparison and Drug Screening of Spike Proteins of Ten SARS-CoV-2 Variants

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Research 2022年第2期2022卷 5-24页

作者： Qiangzhen Yang Xuemin Jian Ali Alamdar Shah Syed Aamir Fahira Chenxiang Zheng zijia Zhu Ke Wang Jinmai Zhang Yangin Wen Zhiqiang Li Dun Pan Tingting Lu Zhuo Wang yongyong shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministryof Education)Shanghai jiao Tong University1954 Huashan RoadShanghai 200030China Biomedical Sciences Insttuteof Qingdao University(Qingdao Branch of SJTU Bio-X Institutes) Qingdao University Qingdao 266003China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai liao Tong University Afliated Sixth People's Hospital.ShanghaiChina The First Afiliated Hospital of Zhengzhou Universily Zhengzhou 450052China Deparment of Psychiary First Teaching Hospital of Xinjiang Medical UniversitUrumqi 830046China

SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and 21H *** acid mutations are enriched in the spike protein of SARS *** plays a crucial role in cell ***,the impact of these mutations on protein structure and function is *** the pathophysiology and pandemic feaures of these SARS-CoV-2 variants requires knowledge of the spike protein ***,we obtained the spike protein structures of 10 main globally endemic SARS CoV-2 strains using *** clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS CoV-2 Delta *** that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein *** analysis of the binding afinities of ACE2-RBD,antibody-NTD,and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against SI NTD and RBD was decreased in the variants,especally the Delta variant compared with the original strain,which may induce the immune evasion of SARS-CoV-2 ***,by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation,we identified multiple compounds that target S1 NTD and RBD,which might contribute towards the development of clinical anti-SARS-CoV-2 *** findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 va riants.

关键词： globally similarity finding

Scrutinizing the causal relationship between schizophrenia and vitamin supplementation:a Mendelian randomization study

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Journal of Bio-X Research 2022年第1期5卷 18-26页

作者： Aamir Fahira Zijia Zhu Zhiqiang Li yongyong shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Collaborative Innovation Center for Brain ScienceShanghai Jiao Tong UniversityShanghai Department of Pharmacy Henan Key Laboratory of Precision Clinical PharmacyThe First Afiliated Hospital of Zhengzhou UniversityZhengzhouHenan Province The Afiliated Hospital of Qingdao University The Biomedical Sciences Institute of Qingdao University(Qingdao Branch of SJTU Bio-X Institutes)Qingdao UniversityQingdaoShandong ProvinceChina

Objective: Observational studies have reported malnutrition and vitamin deficiency in patients with schizophrenia (SZ), which can lead to serious metabolic syndromes and decrease anti-psychiatric drug outcomes. Whereas, vitamin intake along with psychiatric medication can enhance the medication outcomes. However, it is still unknown if SZ induces vitamin deficiency. Herein, we conduct the Mendelian randomization analysis to explore the causal relationship between schizophrenia and vitamins ***: We retrieved the genome-wide summary statistical data for schizophrenia from recent SZ GWAS data (43,175 cases and 65,166 controls) and vitamins supplementation GWAS data from Neale’s GWAS datasets (more than 337,000 samples from the European population) and performed a two-sample Mendelian randomization analysis to determine the causal association of SZ with vitamin supplementation, in addition, we conduct the sensitivity analysis to obtain reliable results and remove confounding ***: SZ have causal relationships with vitamins A, B, C, D, and E (SZ/vitamin A: β = 0.002, se= 0.001, 95% confidence interval (CI): 0.001 to 0.004,P= 1.41E-05, heterogeneityP= 0.4486;SZ/vitamin B: β= 0.004, se= 0.001, 95% CI: 0.002-0.005,P= 7.0E-05, heterogeneityP= 0.2217;SZ/vitamin C: β= 0.004, se= 0.001, 95% CI: 0.002-0.007,P= 0.001, heterogeneityP= 0.1349;SZ/vitamin D: β= 0.003, se= 0.001, 95% CI: 0.002-0.005,P= 0.001, heterogeneityP= 0.433;SZ/vitamin E: β= 0.003, se= 0.001, 95% CI: 0.002-0.005,P= 5.0E-05, heterogeneityP= 0.1382).Conclusion: Our findings suggest that vitamin levels and supplementation should be carefully controlled in patients with SZ, which in turn may enhance the therapeutic effects of antipsychotic drug treatments.

关键词： dietary intake Mendelian randomization study psychiatric disorders unhealthy lifestyle vitamins supplementation

Common SNPs and haplotypes in Satb2 are associated with schizophrenia in the Uygur Chinese Population

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Common SNPs and haplotypes in Satb2 are associated with schi...

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals

2017中国长三角遗传学大会

作者： Juan Zhou Wei Xu Jianhua Chen yongyong shi Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Collaborative Innovation Center for Brain ScienceShanghai Jiao Tong University

Schizophrenia is one of the most severe mental disorders probably caused by multiple susceptibility *** functional studies of Satb2 showed its crucial role in central nervous development,cognition and main pathways implicated schizophrenia pathophysiology.A previous genome-wide association study(GWAS) of schizophrenia has shown that rs6704641 in Satb2 gene was significant associated with *** this study,we performed a case-control study focusing on seven tag SNPs located in Satb2 gene among 985 patients with schizophrenia and 1218 healthy controls recruited from the Uygur Chinese *** found that rs6704641 was significantly associated with schizophrenia in both allele and genotype distributions(Pallele=0.001,Pallele=0.008 after FDR-BH correction,Pgenotye=0.004,Pgenotye=0.028 after FDR-BH correction).In addition,rs16831466 was significantly associated with schizophrenia only in the allele distributions(Pallele=0.011,Pallele=0.041 after FDR-BH correction).In the block rs6704641-rs7600663-rs13028839,two haplotypes were significant associated with *** was a risk factor(A-C-G:corrected P=0.001) and another was a protective factor(G-C-G:corrected P=0.029).In the block rs12052310-rs4673339-rs16831466-rs16831496,three haplotypes were *** of them were risk factors(G-G-C-C:corrected P=0.048;G-A-C-G:corrected P=0.048) while the other one was a protective factor(C-A-A-C:corrected P= 0.027).Our results suggested that Satb2 was also a susceptibility gene for schizophrenia in the Uygur Chinese population,and subsequent functional validation test was needed to be explored in the further study.

关键词： Satb2 schizophrenia association study Uygur Chinese population

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Genome-Wide Association Study of Obstructive Sleep Apnea and...

端粒长度与2型糖尿病:孟德尔随机化研究与多基因风险评分分析

中国睡眠研究会第十五届全国学术年会

作者： Huajun Xu Feng Liu Zhiqiang Li Shankai Yin Jian Guan yongyong shi Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Bio-X center of Shanghai Jiao Tong University

Rationale: Previous genetic studies of obstructive sleep apnea(OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions;thus, the heritability of OSA remains poorly ***: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional ***: A genome-wide association study was performed in 20,590 Han Chinese individuals(5,438 OSA and 15,152 control samples).Human samples and point mutation knockin mice were used for follow-up investigation of gene *** and Main Results: Two characteristic study wide significant loci(P, 2.63 3 1029) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26(odds ratio [OR] = 1.62;95% confidence interval [CI], 1.39–1.89;P = 6.98 3 10210) and the missense variant rs3746804(***267Leu) in the riboflavin transporter SLC52A3 on 20p13(OR = 0.83;95% CI, 0.79–0.88;P = 7.57 3 10210).In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance ***3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological ***: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related *** findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

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遗传 2020年第9期42卷 882-888页

作者：曹岚李志强师咏勇刘赟上海市妇幼保健中心上海200062 青岛大学生物医学研究院(暨上海交通大学Bio-X研究院青岛分院) 青岛266003 上海交通大学Bio-X研究院遗传发育与精神神经疾病教育部重点实验室上海200030 复旦大学生物医学研究院上海200032

多项观察性研究表明,端粒长度缩短与2型糖尿病(type 2 diabetes,T2D)之间存在关联。然而,传统观察性研究结果常受到混杂因素和反向因果关联的影响,端粒长度与T2D是否存在因果关联尚不明确。本研究在中国汉族人群中利用孟德尔随机化(Mend... 详细信息

多项观察性研究表明,端粒长度缩短与2型糖尿病(type 2 diabetes,T2D)之间存在关联。然而,传统观察性研究结果常受到混杂因素和反向因果关联的影响,端粒长度与T2D是否存在因果关联尚不明确。本研究在中国汉族人群中利用孟德尔随机化(Mendelian randomization,MR)和多基因风险评分(polygenic risk score,PRS)方法探索端粒长度与T2D的因果关系。MR研究选取8个与端粒长度相关的独立遗传变异作为工具变量,利用2632例中国汉族人群T2D全基因组关联研究(genome-wide association study,GWAS)数据,检验遗传预测的端粒长度与T2D的关系。利用中国汉族人群GWAS数据,采用PRS分析评价端粒长度PRS与T2D的关系。MR研究共纳入1318例T2D患者和1314例正常对照,逆方差加权、MR-Egger回归、简单中位数和加权中位数法估计的OR值分别为0.78(95%CI:0.36~1.68,P=0.522)、0.23(95%CI:0.01~7.64,P=0.412)、0.60(95%CI:0.28~1.28,P=0.185)和0.64(95%CI:0.31~1.33,P=0.233),遗传预测的较长端粒长度与T2D之间不存在关联。PRS分析未发现端粒长度PRS与T2D显著关联的一致结果。本研究采用MR和PRS方法未发现端粒长度与T2D具有因果关联,后续研究中增大样本量有助于得出更可靠的结论。

关键词：孟德尔随机化多基因风险评分端粒长度 2型糖尿病

Single-Molecule Detection:Identifying the Genotypes of Hepatitis B virus(HBV) with DNA Origami Label

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Single-Molecule Detection:Identifying the Genotypes of Hepat...