Yufeng Shen

Principal investigator, Associate Professor,
Peking University
Baylor College of Medicine
Google Scholar

I'm an Associate Professor at Columbia University in the Department of Systems Biology and Department of Biomedical Informatics.

I received my B.Sc. in biochemistry and molecular biology from Peking University and Ph.D. in computational biology from Baylor College of Medicine. At Baylor, I led the analysis of the first human genome sequenced by next-generation technologies.

I currently directs National Institutes of Health–funded research programs that integrate genomics data to predict consequences of genetic variation using statistical and computational methods and to apply genomics and computational biology in genetic studies of human diseases. My lab developed CANOES (Backenroth et al., Nucleic Acids Res., 2014), a method to identify rare copy number variants from exome sequencing data. We discovered that epigenomic patterns under normal conditions are associated with risk genes of developmental disorders (Han et al., Nat. Commun., 2018). In addition, our research led to the discovery of a number of novel risk genes of common birth defects such as congenital heart disease (Homsy et al., Science, 2015) and congenital diaphragmatic hernia (Qi et al., PLoS Genetics, 2018).

  1. Integration of gene expression data in Bayesian association analysis of rare variants Communications Biology (accepted). 2023
  2. Association of Predicted Damaging De Novo Variants on Ventricular Function in Individuals With Congenital Heart Disease Circulation Genomic and Precision Medicine. 2023
  3. Tissue adaptation and clonal segregation of human memory T cells in barrier sites Nature Immunology. 2023
  4. Predicted loss of function alleles in Bassoon (BSN) are associated with obesity medRxiv. 2023
  5. SHINE: Protein Language Model based Pathogenicity Prediction for Inframe Insertion and Deletion Variants Briefings in Bioinformatics. 2023
  6. Predicting functional effect of missense variants using graph attention neural networks Nature Machine Intelligence. 2022
  7. Accurate in silico confirmation of rare copy number variant calls from exome sequencing data using transfer learning Nucleic acids research. 2022
  8. AlphaCluster: Coevolutionary driven residue-residue interaction models enable quantifiable clustering analysis of de novo variants to enhance predictions of pathogenicity Research Square. 2022
  9. Integrating de novo and inherited variants in over 42,607 autism cases identifies mutations in new moderate risk genes Nature Genetics. 2022
  10. Statistical models of the genetic etiology of congenital heart disease Current Opinion in Genetics & Development. 2022
  11. Newborn screening for neurodevelopmental diseases: Are we there yet? Am J Med Genet. 2022
  12. Identification and validation of novel candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas HGG Advances. 2022
  13. The genetic architecture of pediatric cardiomyopathy AJHG. 2022
  14. Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene AJHG. 2021
  15. Imputing cognitive impairment in SPARK, a large autism cohort Autism Research. 2022
  16. Gene expression atlas of energy balance brain regions JCI Insight. 2021
  17. Predicting localized affinity of RNA binding proteins to transcripts with convolutional neural networks bioRxiv. 2021
  18. Rare variant analysis of 4,241 pulmonary arterial hypertension cases from an international consortium implicate FBLN2, PDGFD and rare de novo variants in PAH Genome Medicine. 2021
  19. Penetrance of breast cancer genes from the eMERGE III Network JNCI Cancer Spectrum. 2021
  20. Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A-associated neurological disorder HGG Advances. 2021
  21. Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells Science Immunology. 2021
  22. Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease JAMA Cardiology. 2021
  23. Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation JCI. 2021
  24. Functional interrogation of DNA damage response variants with base editing screens Cell. 2021
  25. MVP predicts pathogenicity of missense variants by deep learning Nature Communications. 2021
  26. Template-based prediction of protein structure with deep learning BMC Genomics. 2020
  27. Genomic analyses implicate noncoding de novo variants in congenital heart disease Nature Genetics. 2020
  28. Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes Genetics in Medicine. 2020
  29. Novel Candidate Genes in Esophageal Atresia/Tracheoesophageal Fistula Identified by Exome Sequencing EJHG. 2020
  30. Dissecting Autism Genetic Risk Using Single-cell RNA-seq Data bioRxiv. 2020
  31. EM-mosaic detects mosaic point mutations that contribute to congenital heart disease. Genome medicine. 2020
  32. Whole Genome De Novo Variant Identification with FreeBayes and Neural Network Approaches bioRxiv. 2020
  33. Novel Mutations and Decreased Expression of the Epigenetic Regulator TET2 in Pulmonary Arterial Hypertension. Circulation. 2020
  34. Tissue Determinants of Human NK Cell Development, Function, and Residence. Cell. 2020
  35. Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension. Genome medicine. 2019
  36. De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes. Nature communications. 2019
  37. Deletion of donor-reactive T cell clones after human liver transplant. American journal of transplantation. 2019
  38. Pathway analysis of genomic pathology tests for prognostic cancer subtyping. Journal of biomedical informatics. 2019
  39. Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes. NPJ genomic medicine. 2019
  40. Single cell RNA-Seq reveals pre-cDCs fate determined by transcription factor combinatorial dose. BMC molecular and cell biology. 2019
  41. Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions. Clinical pharmacology and therapeutics. 2019
  42. Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire. The Journal of clinical investigation. 2019
  43. Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder. American journal of human genetics. 2019
  44. Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. Clinical pharmacology and therapeutics. 2019
  45. De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders. PLoS genetics. 2018
  46. Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool. Cell stem cell. 2018
  47. Early expansion of donor-specific Tregs in tolerant kidney transplant recipients. JCI insight. 2018
  48. A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveals that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes. BMC medical genomics. 2018
  49. Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension. Circulation. Genomic and precision medicine. 2018
  50. Human Lymph Nodes Maintain TCF-1(hi) Memory T Cells with High Functional Potential and Clonal Diversity throughout Life. Journal of immunology. 2018
  51. Quantifying size and diversity of the human T cell alloresponse. JCI insight. 2018
  52. Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease. Genome medicine. 2018
  53. Distinct epigenomic patterns are associated with haploinsufficiency and predict risk genes of developmental disorders. Nature communications. 2018
  54. Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults. Circulation. Genomic and precision medicine. 2018
  55. Robust identification of mosaic variants in congenital heart disease. Human genetics. 2018
  56. SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research. Neuron. 2018
  57. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nature genetics. 2017
  58. Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell reports. 2017
  59. Congenital diaphragmatic hernias: from genes to mechanisms to therapies. Disease models & mechanisms. 2017
  60. Contrasting Determinants of Mutation Rates in Germline and Soma. Genetics. 2017
  61. Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors. Nature immunology. 2017
  62. Longterm maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites. Science immunology. 2017
  63. Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. Human genetics. 2017
  64. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Science immunology. 2017
  65. Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study. Gastroenterology. 2017
  66. A Cell Type-Specific Expression Signature Predicts Haploinsufficient Autism-Susceptibility Genes. Human mutation. 2016
  67. Loss of RNA expression and allele-specific expression associated with congenital heart disease. Nature communications. 2016
  68. Rare variant phasing and haplotypic expression from RNA sequencing with phASER. Nature communications. 2016
  69. Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. American journal of human genetics. 2016
  70. De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia. Journal of medical genetics. 2016
  71. Deep Genetic Connection Between Cancer and Developmental Disorders. Human mutation. 2016
  72. Long-read sequencing and de novo assembly of a Chinese genome. Nature communications. 2016
  73. Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire. PNAS. 2016
  74. A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects. Neurogenetics. 2016
  75. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenetics and genomics. 2016
  76. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science. 2015
  77. A New Window into the Human Alloresponse. Transplantation. 2016
  78. SeqMule: automated pipeline for analysis of human exome/genome sequencing data. Scientific reports. 2015
  79. RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states. BMC medical genomics. 2015
  80. Mutations in ARID2 are associated with intellectual disabilities. Neurogenetics. 2015
  81. Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations. Journal of clinical oncology. 2015
  82. The support of human genetic evidence for approved drug indications. Nature genetics. 2015
  83. ABC transporters and the proteasome complex are implicated in susceptibility to Stevens-Johnson syndrome and toxic epidermal necrolysis across multiple drugs. PloS one. 2015
  84. Genomic signatures of cooperation and conflict in the social amoeba. Current biology. 2015
  85. Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia. Human molecular genetics. 2015
  86. Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients. Science translational medicine. 2015
  87. Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors. Cell stem cell. 2014
  88. Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell. 2014
  89. Coding mutations in SORL1 and Alzheimer disease. Annals of neurology. 2014
  90. Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data. Circulation research. 2014
  91. Estimating heritability of drug-induced liver injury from common variants and implications for future study designs. Scientific reports. 2014
  92. CANOES: detecting rare copy number variants from whole exome sequencing data. Nucleic acids research. 2014
  93. Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia. Journal of medical genetics. 2014
  94. Novel association of early onset hepatocellular carcinoma with transaldolase deficiency. JIMD reports. 2013
  95. Defining a comprehensive verotype using electronic health records for personalized medicine. Journal of the American Medical Informatics Association. 2013
  96. A collaborative approach to developing an electronic health record phenotyping algorithm for drug-induced liver injury. Journal of the American Medical Informatics Association. 2013
  97. Whole-exome sequencing identifies novel LEPR mutations in individuals with severe early onset obesity. Obesity. 2013
  98. Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis. PNAS. 2013
  99. Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. Human genetics. 2012
  100. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Pharmacogenetics and genomics. 2012
  101. Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. The oncologist. 2012
  102. A hidden Markov model for copy number variant prediction from whole genome resequencing data. BMC bioinformatics. 2011
  103. Coverage tradeoffs and power estimation in the design of whole-genome sequencing experiments for detecting association. Bioinformatics. 2011
  104. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011
  105. Genome-wide association study of serious blistering skin rash caused by drugs. The pharmacogenomics journal. 2011
  106. A SNP discovery method to assess variant allele probability from next-generation resequencing data. Genome research. 2009
  107. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature genetics. 2009
  108. Bos taurus genome assembly. BMC genomics. 2009
  109. Comparing platforms for C. elegans mutant identification using high-throughput whole-genome sequencing. PloS one. 2008
  110. A high-throughput percentage-of-binding strategy to measure binding energies in DNA-protein interactions: application to genome-scale site discovery. Nucleic acids research. 2008
  111. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008
  112. Evolutionary and biomedical insights from the rhesus macaque genome. Science. 2007
  113. Shedding genomic light on Aristotle's lantern. Developmental biology. 2006
  114. Conformational pathways in the gating of Escherichia coli mechanosensitive channel. PNAS. 2002
  115. Intrinsic flexibility and gating mechanism of the potassium channel KcsA. PNAS. 2002