Xiaoxu Yang, Ph.D
Center for Bioinformatics, Peking University
Room 314, Wangkezhen Building, No.5 Yiheyuan Road, Haidian District
Beijing, P.R.China 100871
Email: yangxx@mail.cbi.pku.edu.cn
ORCID: 0000-0003-0219-0023
Education
Ph.D. in Bioinformatics, School of Life Sciences, Peking University, Beijing, China 2013-2018
Dissertation topic: Role of mosaicism in the genetics of childhood neurological and psychiatric disorders.
Advisor: Prof. Liping Wei
B.S. in Biological Science, College of Life Sciences, Beijing Normal University, Beijing, China 2009-2013
Undergraduate student in Information Science and Technology, College of Information Science and Technology, Beijing Normal University, Beijing, China 2008-2009
Research Experience
Graduated Research Assistant, Peking University, Beijing, China 2013-present
- Established the postzygotic mutation validation and quantification frameworks capable for genetic screen: developed PASM, the first amplicon deep semiconductor resequencing pipeline coupled with a Bayesian-model for quantification and validation of post-zygotic mosaicism with allele fractions as low as 0.5%; firstly utilized mDDPCR, a micro-droplet digital PCR based detection and quantification pipeline for ultra-low-fraction (0.01%) mosaicism in non-cancer disorders.
- Identified approximately 10% of parental mosaicism for seemingly “de novo” SCN1A mutations in 174 Chinese Dravet syndrome families using PASM and mDDPCR; quantified significantly higher mutant allele fractions (MAFs) in mosaic parents with epileptic phenotype than in those without; discovered that the MAFs of genomic mosaicisms in paternal sperms are significantly elevated than in their blood for the first time in a cancer gene-unrelated disease cohort.
- Firstly identified parental ATP1A3 mosaicism in 6 out of 80 alternating hemiplegia of childhood (AHC) families using mDDPCR and PASM; discovered the MAF geographical imbalance and potential directional selection in cultured fibroblasts from AHC mosaic parents; carried out a large systematic study of PCDH19 and MECP2 mosaic mutation profiles in 146 Chinese families.
- Participated in the development and improvement for MosaicHunter, the first Bayesian-based bioinformatics tool for identifying postzygotic mutations in control-free whole-genome or whole-exome sequencing of non-cancer individuals (http://mosaichunter.cbi.pku.edu.cn/); evaluated the high accuracy of MosaicHunter on real data with PASM.
- Participated in the detection of the prevalence, mutational signature of 1533 pSNMs from WES data in 2,374 Autism Spectrum Disorder (ASD) families using MosaicHunter; accurately validated and quantified the MAFs of 447 ASD related mosaic mutations using improved PASM which showed higher throughput and lower sequencing error; among the first to demonstrate that higher mosaic MAFs contributed to ASD diagnoses and phenotypic influences.
- Participated in the development and benchmarking of o2n-seq, an ultra-sensitive and high-efficiency screening method for de novo low-frequency mutations, the Bayesian model of PASM greatly improved the detection limit for customized Ampliseq panels to under 0.1% and mDDPCR was proved to be the only ultra-low fraction detection method independent of sequencing comparable to o2n-seq at 0.001% level.
- Participated in the first whole-genome scale identification of postzygotic single-nucleotide mosaicisms of three clinically unremarkable adults, provided solid validation of 38 mosaic candidates using clonal Sanger sequencing; participated in the first landscape description of mosaicism from whole genome sequences of 20 postmortem tissues of five clinically unremarkable individuals, validated 244 mosaic candidates using improved PASM which is capable for more than 2,000 samples at a single run. Validated the two types of postzygotic single nucleotide mosaicism – embryonic mosaicism and clonal expansion mosaicism from multiple human samples.
- Participated in the collection of 300 Chinese children and families with ASD and the collection of 156 Chinese control samples; conducted behavior questionnaires and surveys of children and parents in 18 families with ASD and 156 controls;
Honors
Excellent Graduate, Peking University 2018
The president’s scholarship, Peking University 2013, 2014, 2015, 2016, 2017
Doctorate Academic Excellence Scholarship, Peking University 2015, 2017
Outstanding Graduate, Education Committee of Beijing, Beijing 2013
The second prize of Li Yun Scholarship, Beijing Normal University, Beijing 2012
National Scholarship, Ministry of Education, China 2011
Merit Student, Education Committee of Beijing, Beijing 2011
The first prize in National English Contest for College Students, National Foreign Language Teaching Advisory Board, China 2010
Merit Student, Beijing Normal University, Beijing 2009-2013
Membership
Trainee member, The American Society of Human Genetics, MD, USA 2017
Publications
Yang X*, Liu A*, Xu X, Yang X, Zeng Q, Ye AY , Yu Z, Wang S, Huang AY, Wu X, et al. 2017. Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort. Sci. Rep. DOI: 10.1038/s41598-017-15814-7.
Xu X*, Yang X*, Wu Q*, Liu A, Yang X, Ye AY, Huang AY, Li J, Wang M, Yu Z, et al. 2015. Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of ‘de novo’ SCN1A Mutations in Children with Dravet Syndrome. Hum. Mutat. 36(9):861-72. DOI: 10.1002/humu.22819.
Huang AY*, Yang X*, Wang S, Zheng X, Wu Q, Ye AY, Wei L. 2018. Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs. PLOS Genet. DOI: 10.1371/journal.pgen.1007395.
Liu A*, Yang X*, Yang X*, Wu Q, Zhang J, Xu X, et al. Postzygotic mosaicism and variable penetrance of PCDH19 mutations in a Chinese cohort. J. Med. Genet. ( in revision)
Yang X*, Yang X*, Li S, Zeng Q, Zhang J, Huang AY, et al. ATP1A3 mosaicism in families with alternating hemiplegia of childhood. Euro. J. Hum. Genet. (in revision)
Ding Y*, Yang X*, Zhao W, Zhang T, Xu F, Zhang M, Zeng C, et al. Detection of postzygotic single-nucleotide mosaicisms of complement genes in patients with rare nephropathies. Genetics. (In submission)
Dou Y, Yang X, Li Z, Wang S, Zhang Z, Ye AY, Yan L, Yang C, Wu Q, Li J, et al. 2017. Post-zygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations. Hum. Mutat. (cover article) DOI: 10.1002/humu.23255.
Liu A, Yang X, Xu X, Wu Q, Tian X, Yang X, Wu X, Wei L, Zhang Y. 2017. Study on mosaicism of SCN1A gene mutation in parents of children with Dravet syndrome. Chinese J. Pediatrics. 2;55(11):818-823. DOI: 10.3760/cma.j.issn.0578-1310.2017.11.005.
Ye AY*, Dou Y*, Yang X, Wang S, Huang AY, Wei L. 2018. A Model for Postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations. Genome Res. DOI:10.1101/gr.230003.117.
Wang K, Lai S, Yang X, Zhu T, Lu X, Wu C, Ruan J. 2017. Ultrasensitive and high-efficiency screen of de novo low-frequency mutations by o2n-seq. Nat. Comms. 8:15335. DOI: 10.1038/ncomms15335.
Yang C, Li J, Wu Q, Yang X, Huang AY, Zhang J, Ye AY, et al. AutismKB 2.0: a knowledgebase for the genetic evidence of autism spectrum disorder. Database. (Under review)
Ding Y, Wang M, He Y, Ye AY, Yang X, Liu F, Meng Y, Gao G, Wei L. 2014. "Bioinformatics: introduction and methods," a bilingual Massive Open Online Course (MOOC) as a new example for global bioinformatics education. PLoS Comput. Biol. 10(12):e1003955. DOI: 10.1371/journal.pcbi.1003955.
Huang AY*, Zhang Z*, Ye AY*, Dou Y*, Yan L, Yang X, Zhang Y, Wei L. 2017. MosaicHunter: accurate detection of postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples. Nucleic Acids Res. DOI: 10.1093/nar/gkx024.
Zhao B, Wu Q, Ye AY, Guo J, Zheng X, Yang X, Liu Q, et al. Shaped somatic LINE-1 retrotransposition in cortical neurons of Rett patients and healthy individuals. Genome Res.(In revision)
Zhang J, Li Z, Wu Y, Ye AY, Chen L, Yang X, Wu Q, and Wei L., Analysis of deficits in responding to joint attention cues in autism spectrum disorder using automated analyses of eye tracking data. Mol. Autism. (In submission)
Huang AY*, Xu X*, Ye AY*, Wu Q*, Yan L, Zhao B, Yang X, He Y, Wang S, Zhang Z, et al. 2014. Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals. Cell Res. 24(11):1311-27. (cover article) DOI:10.1038/cr.2014.131.
Jiang S*, Cheng S*, Ren L, Kang Y, Ding Y, Hou M, Yang X, Lin Y, et al. An expanded landscape of human long noncoding RNA. Genome. Res.(Under review)
(*equal contributions)
Presentations
Platform presentation, “Deep amplicon resequencing identified parental mosaicism for approximately 10% “de novo” SCN1A mutations in Dravet Syndrome families and was capable of multiple validation of mosaicism”, The American Society of Human Genetics 2017 Annual Meeting, Orlando, Florida, October 2017
Platform presentation, “Low-fraction parental mosaicism in SCN1A de novo mutation families affected with Dravet Syndrome”, Digital PCR and Microfluidic system user conference, EMTD Co. Ltd. and RainDance Technologies, Beijing, China, October 2015
Platform presentation, “Approximately 10% of “de novo” SCN1A mutations causing Dravet Syndrome are inherited from undetected parental mosaicism”, 31st International Epilepsy Congress (IEC), International League Against Epilepsy (ILAE), Istanbul, Turkey, September 2015
Grants
Led the project “The role of mosaicism in the genetics of childhood neurological disorders such as Dravet syndrome and Alternating hemiplegia of childhood”, RMB 9,000, No. 14565, The 24th open testing fund by the School of Life Sciences, Peking University, supervised by Prof. Liping Wei from the Center for Bioinformatics, Peking University, 2016
Participated in “The identification and quantification of human genomic mosaicism and development of bioinformatic methodology and data mining for mutational mechanisms”, RMB 2,740,000, No 31530092, the Key Research Project of the National Natural Science Foundation, Led by Prof. Liping Wei from the Center for Bioinformatics, Peking University, 2016- current
Led the project “The role of protein degradation in the process of aging yeast”, RMB 20,000, The National Undergraduate Innovative Experiment Program, supervised by Prof. Xiaobo Qiu from the institute of cell biology, Beijing Normal University, 2011-2012.
Workshops and Short Courses Completed
“Human Genetics: Linkage Analysis and disease genetics”, a summer course given by Drs. Jurg Ott (Rockefeller University), Marcella Devoto (University of Pennsylvania), Yaning Yang (University of Science and Technology of China) and Dawei Li (University of Vermont), Peking University, Beijing, China, August 2017
“Human Genetics: Linkage Analysis and disease genetics”, a summer course given by Drs. Jurg Ott (Rockefeller University), Marcella Devoto (University of Pennsylvania), Andrew DeWan (Yale University) and Stephan Sanders (University of California, San Francisco), Peking University, Beijing, China, August 2015
“Advanced Biostatistics Short Course”, a short course given by Dr. Yu Shyr (Vanderbilt University), National Institute of Biological Sciences, Beijing, China, April 2015
“Human Genetics: Linkage Analysis”, a summer course given by Drs. Jurg Ott (Rockefeller University), Suzanne Leal (Baylor College of Medicine), Andrew DeWan (Yale University) (University of California, San Francisco), Peking University, Beijing, China, July 2014
“Advanced Biostatistics with Case Studies and R”, a short course given by Dr. Yu Shyr (Vanderbilt University), National Institute of Biological Sciences, Beijing, China, April 2014
“Advanced Biostatistics with R - Design & Data Analysis with Case Studies”, a workshop given by Dr. Yu Shyr, National Institute of Biological Sciences, Beijing, China, April 2013
Teaching and Mentoring
Supervisor of Undergraduate Students, literature mining, bioinformatic and biostatistical analysis for non-cancer disease related mosaicism (Yutian Tao and Luoxing Xiong, 4th year undergraduate students), School of Life Sciences, Peking University 2013-2014
Teaching assistant, “Human Genetics: linkage analysis and disease genetics”, Peking University 2017 Teaching assistant, “PTN Bioinformatic Track”, Peking University – Tsinghua University - National Institute of Biological Sciences joint program 2016
Teaching assistant, “Methods in Bioinformatics”, Peking University 2014-2015
Teaching assistant, “Bioinformatics: Introduction and Methods”, MOOC on Coursera 2013-2015
Teaching assistant, “Biostatistics”, Peking University 2013-2014
Technical Skills
Dry lab skills:
C and C++ programming.
R programming, data analysis and presentation.
Linux shell scripting and Perl scripting.
NGS data analysis and quality control using GATK and MosaicHunter, multiple annotations and variant predictions.
Scientific computing on high-performance supercomputers (HPCs).
Wet lab skills:
NGS library preparations and quality controls of large sample size.
Use of Illumina MiSeq sequencer, use of Ion Torrent PGM and S5 sequencers.
Use of RainDance digital PCR systems, use of Perkin Elmer robot arms for large sample size.
Gel electrophoresis, DNA/RNA extraction in multiple tissues and samples, PCR, qPCR, western plot, cell culture, transfection, transformations, ligations.
Languages
Proficient in English
Native speaker of Chinese