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 direct 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. PreMode predicts mode of action of missense variants by deep graph representation learning of protein sequence and structural context bioRxiv. 2024
  2. Functional dissection of human cardiac enhancers and noncoding de novo variants in congenital heart disease Nature Genetics. 2024
  3. Rescuing lung development through embryonic inhibition of histone acetylation Science Translational Medicine. 2024
  4. A probabilistic graphical model for estimating selection coefficient of nonsynonymous variants from human population sequence data medRxiv. 2023
  5. Disrupted endosomal trafficking of the Vangl-Celsr polarity complex underlies congenital anomalies in trachea-esophageal morphogenesis bioRxiv. 2023
  6. SABRE: Self-Attention Based model for predicting T-cell Receptor Epitope Specificity bioRxiv. 2023
  7. VBASS enables integration of single cell gene expression data in Bayesian association analysis of rare variants Communications Biology. 2023
  8. Association of Predicted Damaging De Novo Variants on Ventricular Function in Individuals With Congenital Heart Disease Circulation Genomic and Precision Medicine. 2023
  9. Tissue adaptation and clonal segregation of human memory T cells in barrier sites Nature Immunology. 2023
  10. Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity npj Genomic Medicine. 2023
  11. SHINE: Protein Language Model based Pathogenicity Prediction for Inframe Insertion and Deletion Variants Briefings in Bioinformatics. 2023
  12. Predicting functional effect of missense variants using graph attention neural networks Nature Machine Intelligence. 2022
  13. Accurate in silico confirmation of rare copy number variant calls from exome sequencing data using transfer learning Nucleic acids research. 2022
  14. AlphaCluster: Coevolutionary driven residue-residue interaction models enable quantifiable clustering analysis of de novo variants to enhance predictions of pathogenicity Research Square. 2022
  15. Integrating de novo and inherited variants in over 42,607 autism cases identifies mutations in new moderate risk genes Nature Genetics. 2022
  16. Statistical models of the genetic etiology of congenital heart disease Current Opinion in Genetics & Development. 2022
  17. Newborn screening for neurodevelopmental diseases: Are we there yet? Am J Med Genet. 2022
  18. Identification and validation of novel candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas HGG Advances. 2022
  19. The genetic architecture of pediatric cardiomyopathy AJHG. 2022
  20. Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene AJHG. 2021
  21. Imputing cognitive impairment in SPARK, a large autism cohort Autism Research. 2022
  22. Gene expression atlas of energy balance brain regions JCI Insight. 2021
  23. Predicting localized affinity of RNA binding proteins to transcripts with convolutional neural networks bioRxiv. 2021
  24. 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
  25. Penetrance of breast cancer genes from the eMERGE III Network JNCI Cancer Spectrum. 2021
  26. Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A-associated neurological disorder HGG Advances. 2021
  27. Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells Science Immunology. 2021
  28. Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease JAMA Cardiology. 2021
  29. Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation JCI. 2021
  30. Functional interrogation of DNA damage response variants with base editing screens Cell. 2021
  31. MVP predicts pathogenicity of missense variants by deep learning Nature Communications. 2021
  32. Template-based prediction of protein structure with deep learning BMC Genomics. 2020
  33. Genomic analyses implicate noncoding de novo variants in congenital heart disease Nature Genetics. 2020
  34. Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes Genetics in Medicine. 2020
  35. Novel Candidate Genes in Esophageal Atresia/Tracheoesophageal Fistula Identified by Exome Sequencing EJHG. 2020
  36. Dissecting Autism Genetic Risk Using Single-cell RNA-seq Data bioRxiv. 2020
  37. EM-mosaic detects mosaic point mutations that contribute to congenital heart disease. Genome medicine. 2020
  38. Whole Genome De Novo Variant Identification with FreeBayes and Neural Network Approaches bioRxiv. 2020
  39. Novel Mutations and Decreased Expression of the Epigenetic Regulator TET2 in Pulmonary Arterial Hypertension. Circulation. 2020
  40. Tissue Determinants of Human NK Cell Development, Function, and Residence. Cell. 2020
  41. Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension. Genome medicine. 2019
  42. De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes. Nature communications. 2019
  43. Deletion of donor-reactive T cell clones after human liver transplant. American journal of transplantation. 2019
  44. Pathway analysis of genomic pathology tests for prognostic cancer subtyping. Journal of biomedical informatics. 2019
  45. Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes. NPJ genomic medicine. 2019
  46. Single cell RNA-Seq reveals pre-cDCs fate determined by transcription factor combinatorial dose. BMC molecular and cell biology. 2019
  47. Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions. Clinical pharmacology and therapeutics. 2019
  48. Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire. The Journal of clinical investigation. 2019
  49. 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
  50. Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. Clinical pharmacology and therapeutics. 2019
  51. De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders. PLoS genetics. 2018
  52. Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool. Cell stem cell. 2018
  53. Early expansion of donor-specific Tregs in tolerant kidney transplant recipients. JCI insight. 2018
  54. 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
  55. Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension. Circulation. Genomic and precision medicine. 2018
  56. Human Lymph Nodes Maintain TCF-1(hi) Memory T Cells with High Functional Potential and Clonal Diversity throughout Life. Journal of immunology. 2018
  57. Quantifying size and diversity of the human T cell alloresponse. JCI insight. 2018
  58. Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease. Genome medicine. 2018
  59. Distinct epigenomic patterns are associated with haploinsufficiency and predict risk genes of developmental disorders. Nature communications. 2018
  60. Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults. Circulation. Genomic and precision medicine. 2018
  61. Robust identification of mosaic variants in congenital heart disease. Human genetics. 2018
  62. SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research. Neuron. 2018
  63. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nature genetics. 2017
  64. Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell reports. 2017
  65. Congenital diaphragmatic hernias: from genes to mechanisms to therapies. Disease models & mechanisms. 2017
  66. Contrasting Determinants of Mutation Rates in Germline and Soma. Genetics. 2017
  67. Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors. Nature immunology. 2017
  68. Longterm maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites. Science immunology. 2017
  69. Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. Human genetics. 2017
  70. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Science immunology. 2017
  71. 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
  72. A Cell Type-Specific Expression Signature Predicts Haploinsufficient Autism-Susceptibility Genes. Human mutation. 2016
  73. Loss of RNA expression and allele-specific expression associated with congenital heart disease. Nature communications. 2016
  74. Rare variant phasing and haplotypic expression from RNA sequencing with phASER. Nature communications. 2016
  75. Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. American journal of human genetics. 2016
  76. De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia. Journal of medical genetics. 2016
  77. Deep Genetic Connection Between Cancer and Developmental Disorders. Human mutation. 2016
  78. Long-read sequencing and de novo assembly of a Chinese genome. Nature communications. 2016
  79. Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire. PNAS. 2016
  80. A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects. Neurogenetics. 2016
  81. HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury. Pharmacogenetics and genomics. 2016
  82. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science. 2015
  83. A New Window into the Human Alloresponse. Transplantation. 2016
  84. SeqMule: automated pipeline for analysis of human exome/genome sequencing data. Scientific reports. 2015
  85. RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states. BMC medical genomics. 2015
  86. Mutations in ARID2 are associated with intellectual disabilities. Neurogenetics. 2015
  87. Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations. Journal of clinical oncology. 2015
  88. The support of human genetic evidence for approved drug indications. Nature genetics. 2015
  89. ABC transporters and the proteasome complex are implicated in susceptibility to Stevens-Johnson syndrome and toxic epidermal necrolysis across multiple drugs. PloS one. 2015
  90. Genomic signatures of cooperation and conflict in the social amoeba. Current biology. 2015
  91. Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia. Human molecular genetics. 2015
  92. Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients. Science translational medicine. 2015
  93. Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors. Cell stem cell. 2014
  94. Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell. 2014
  95. Coding mutations in SORL1 and Alzheimer disease. Annals of neurology. 2014
  96. 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
  97. Estimating heritability of drug-induced liver injury from common variants and implications for future study designs. Scientific reports. 2014
  98. CANOES: detecting rare copy number variants from whole exome sequencing data. Nucleic acids research. 2014
  99. Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia. Journal of medical genetics. 2014
  100. Novel association of early onset hepatocellular carcinoma with transaldolase deficiency. JIMD reports. 2013
  101. Defining a comprehensive verotype using electronic health records for personalized medicine. Journal of the American Medical Informatics Association. 2013
  102. A collaborative approach to developing an electronic health record phenotyping algorithm for drug-induced liver injury. Journal of the American Medical Informatics Association. 2013
  103. Whole-exome sequencing identifies novel LEPR mutations in individuals with severe early onset obesity. Obesity. 2013
  104. Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis. PNAS. 2013
  105. Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. Human genetics. 2012
  106. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Pharmacogenetics and genomics. 2012
  107. Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. The oncologist. 2012
  108. A hidden Markov model for copy number variant prediction from whole genome resequencing data. BMC bioinformatics. 2011
  109. Coverage tradeoffs and power estimation in the design of whole-genome sequencing experiments for detecting association. Bioinformatics. 2011
  110. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011
  111. Genome-wide association study of serious blistering skin rash caused by drugs. The pharmacogenomics journal. 2011
  112. A SNP discovery method to assess variant allele probability from next-generation resequencing data. Genome research. 2009
  113. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature genetics. 2009
  114. Bos taurus genome assembly. BMC genomics. 2009
  115. Comparing platforms for C. elegans mutant identification using high-throughput whole-genome sequencing. PloS one. 2008
  116. 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
  117. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008
  118. Evolutionary and biomedical insights from the rhesus macaque genome. Science. 2007
  119. Shedding genomic light on Aristotle's lantern. Developmental biology. 2006
  120. Conformational pathways in the gating of Escherichia coli mechanosensitive channel. PNAS. 2002
  121. Intrinsic flexibility and gating mechanism of the potassium channel KcsA. PNAS. 2002