About

Cedric Feschotte is a Professor in the Department of Molecular Biology and Genetics at Cornell University. He is a member of the Graduate Fields of Genetics, Genomics and Development, as well as Biochemistry, Molecular and Cell Biology. Dr. Feschotte's laboratory specializes in studying mobile genetic elements, such as transposons and endogenous viruses, primarily within vertebrate genomes, including humans. With over 20 years of experience, his research employs an integrative approach combining functional and computational genomics, biochemistry, and genetics in model systems like zebrafish and cell culture. The overarching goal of his work is to characterize the impact of mobile genetic elements on the evolution and physiology of their host species, including their roles in disease states. His research explores how these elements have contributed to biological novelty during evolution, particularly through the remodeling of processes such as innate immunity and development, and investigates the mechanisms underlying their propagation and long-term influence on genome architecture and complexity.

Research topics

• Genetics
• Biology
• Evolutionary biology
• Ecology

Selected publications

• Complete sequencing of ape genomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2024 · 25 citations

  • Biology
  • Evolutionary biology
  • Genetics

  We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. We resolve challenging regions, such as the major histocompatibility complex and immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate the evolution and diversity of regions previously uncharacterized or incompletely studied without bias from mapping to the human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, and subterminal heterochromatin. This resource should serve as a definitive baseline for all future evolutionary studies of humans and our closest living ape relatives.

  PublisherOA PDFDOI

• Transposable Element Interactions Shape the Ecology of the Deer Mouse Genome

  Molecular Biology and Evolution · 2023 · 30 citations

  • Biology
  • Evolutionary biology
  • Ecology

  The genomic landscape of transposable elements (TEs) varies dramatically across species, with some TEs demonstrating greater success in colonizing particular lineages than others. In mammals, long interspersed nuclear element (LINE) retrotransposons are typically more common than any other TE. Here, we report an unusual genomic landscape of TEs in the deer mouse, Peromyscus maniculatus. In contrast to other previously examined mammals, long terminal repeat elements occupy more of the deer mouse genome than LINEs (11% and 10%, respectively). This pattern reflects a combination of relatively low LINE activity and a massive invasion of lineage-specific endogenous retroviruses (ERVs). Deer mouse ERVs exhibit diverse origins spanning the retroviral phylogeny suggesting they have been host to a wide range of exogenous retroviruses. Notably, we trace the origin of one ERV lineage, which arose ∼5-18 million years ago, to a close relative of feline leukemia virus, revealing inter-ordinal horizontal transmission. Several lineage-specific ERV subfamilies have very high copy numbers, with the top five most abundant accounting for ∼2% of the genome. We also observe a massive amplification of Kruppel-associated box domain-containing zinc finger genes, which likely control ERV activity and whose expansion may have been facilitated by ectopic recombination between ERVs. Finally, we find evidence that ERVs directly impacted the evolutionary trajectory of LINEs by outcompeting them for genomic sites and frequently disrupting autonomous LINE copies. Together, our results illuminate the genomic ecology that shaped the unique deer mouse TE landscape, shedding light on the evolutionary processes that give rise to variation in mammalian genome structure.

  PublisherOA PDFDOI

• A comprehensive SARS-CoV-2–human protein–protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets

  Nature Biotechnology · 2022 · 196 citations

  • Computational biology
  • Biology
  • Virology
  PublisherOA PDFDOI

• Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn’s Disease Patients

  Cellular and Molecular Gastroenterology and Hepatology · 2022 · 56 citations

  • Biology
  • Cell biology
  • Immunology

  BACKGROUND & AIMS: The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non-inflammatory bowel disease control patients. METHODS: Colonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non-inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types. RESULTS: Our analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type-specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type-specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes. CONCLUSIONS: Single-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD.

  DOI

• RepeatModeler2 for automated genomic discovery of transposable element families

  Proceedings of the National Academy of Sciences · 2020 · 3894 citations

  • Computer Science
  • Computational biology
  • Biology

  (rice). In these three species, RepeatModeler2 identified approximately 3 times more consensus sequences matching with >95% sequence identity and sequence coverage to the manually curated sequences than the original RepeatModeler. As expected, the greatest improvement is for LTR retroelements. Thus, RepeatModeler2 represents a valuable addition to the genome annotation toolkit that will enhance the identification and study of TEs in eukaryotic genome sequences. RepeatModeler2 is available as source code or a containerized package under an open license (https://github.com/Dfam-consortium/RepeatModeler, http://www.repeatmasker.org/RepeatModeler/).

  DOI

Frequent coauthors

• Agnes P. Chan

  Translational Genomics Research Institute

  3 shared

• Christine R. Beck

  Institute for Systems Biology

  3 shared

• Yafei Mao

  Wuhan University of Technology

  3 shared

• Nicholas J. Schork

  Translational Genomics Research Institute

  3 shared

• Riley J. Mangan

  Vassar College

  3 shared

• Miriam K. Konkel

  Greenwood Genetic Center

  3 shared

• Mark Loftus

  Clemson University

  3 shared

• Rachel J. O’Neill

  University of Connecticut

  2 shared

Labs

• Feschotte LabPI

Awards & honors

• Inaugural CALS Faculty and Staff Awards (2024)

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