About

Our laboratory develops computational methods for genome sequence analysis. We are particularly interested in methods for identifying remote evolutionary relationships between distantly related protein and RNA sequences.

Research topics

• Genetics
• Biology
• Computational biology
• Computer Science
• Evolutionary biology
• Artificial Intelligence
• Neuroscience

Selected publications

• HMMER web server: 2026 update

  Nucleic Acids Research · 2026-04-15

  articleOpen access

  The HMMER web server, available at https://www.ebi.ac.uk/Tools/hmmer, provides online access to tools from the HMMER software suite (http://hmmer.org/) for protein analysis using profile hidden Markov models. Users can perform sequence similarity searches against a range of regularly updated protein sequence databases or annotate protein sequences with domains and families using profile HMM libraries from protein family databases. Since the 2018 update, the continued exponential growth of sequence databases has necessitated substantial infrastructural improvements to maintain search performance speed and service reliability. To achieve this, the web interface has been completely reengineered using modern web technologies (JavaScript and React), providing users with an enhanced experience, including session-based search history and streamlined results visualization. The web application programming interface has been rewritten to better support programmatic access with updated endpoints and JSON-based responses. The infrastructure has been redesigned to efficiently handle searches against much larger databases through horizontal scaling and asynchronous job processing. Target database offerings have been updated to reflect current usage patterns and data availability. The HMMER web server is free and open to all users, and there is no login requirement.

  PublisherDOI

• Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  eLife · 2025-04-07 · 5 citations

  articleOpen access

  Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice ( Peromyscus maniculatus and P. polionotus ) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus , a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  eLife · 2025-02-27

  preprintOpen access

  Abstract Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• Presence of group II introns in phage genomes

  Nucleic Acids Research · 2025-07-27 · 4 citations

  articleOpen accessSenior author

  Although bacteriophage genomes are under strong selective pressure for high coding density, they are still frequently invaded by mobile genetic elements (MGEs). Group II introns are MGEs that reduce host burden by autocatalytically splicing out of an RNA precursor. While widely known in bacterial, archaeal, and eukaryotic organellar genomes, group II introns have been considered absent in phage. Identifying group II introns in genome sequences has previously been challenging because of their lack of primary sequence similarity. Advances in RNA structure-based homology searches using covariance models has provided the ability to identify the conserved secondary structures of group II introns. Here, we discover that group II introns are widely found in phages from diverse phylogenetic backgrounds, from endosymbiont phage to jumbophage.

  PublisherOA PDFDOI

• Prevalence of Group II Introns in Phage Genomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-23

  preprintOpen accessSenior authorCorresponding

  Although bacteriophage genomes are under strong selective pressure for high coding density, they are still frequently invaded by mobile genetic elements (MGEs). Group II introns are MGEs that reduce host burden by autocatalytically splicing out of RNA before translation. While widely known in bacterial, archaeal, and eukaryotic organellar genomes, group II introns have been considered absent in phage. Identifying group II introns in genome sequences has previously been challenging because of their lack of primary sequence similarity. Advances in RNA structure-based homology searches using covariance models has provided the ability to identify the conserved secondary structures of group II introns. Here, we discover that group II introns are widely prevalent in phages from diverse phylogenetic backgrounds, from endosymbiont phage to jumbophage.

  PublisherOA PDFDOI

• Author response: Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  2025-04-07

  peer-reviewOpen access

  Single-nucleus RNA-sequencing of the hypothalamic preoptic area of monogamous and promiscuous deer mouse species reveals neuronal differences that may be responsible for innate changes in mating and parental care behavior.

  PublisherDOI

• Induction of menstruation in mice reveals the regulation of menstrual shedding

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09 · 5 citations

  preprintOpen access

  During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this compartmentalization has been hindered by the lack of suitable animal models, as mice and rats do not menstruate. Here, we present transgenic mouse models that recapitulate the key anatomical, functional, and transcriptional features of human menstruation through targeted chemogenetic activation of premenstrual differentiation. Using single-cell spatial transcriptomics, we define a new paradigm for spatially regulated fibroblast differentiation that drives pre-menstrual endometrial layering and ultimately determines the extent of tissue shedding. Our results revise a century-old view of endometrial shedding and regeneration and establish new transgenic mice as powerful tools to advance menstruation research.

  PublisherOA PDFDOI

• Author response: Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  2025-02-27

  peer-reviewOpen access

  Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• Author response: Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  2024-11-18

  peer-reviewOpen access

  Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic medial preoptic area (MPOA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the MPOA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our MPOA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherOA PDFDOI

• Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  eLife · 2024-11-18

  preprintOpen access

  Abstract Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic medial preoptic area (MPOA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the MPOA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our MPOA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

Recent grants

• NIH Grant R01HG001363

  NIH · $2.3M · 2008

• NIH Grant F32GM016932

  NIH · $14k

• Institutional Training Grant in Genomic Science

  NIH · $8.4M · 1997–2030

• HMMER and Infernal: Finding distant homologs of sequences and RNA structures

  NIH · $4.3M · 2016–2026

Frequent coauthors

• ROBERT FINN

  European Bioinformatics Institute

  77 shared

• Lawrence B. Holzman

  University of Pennsylvania

  72 shared

• Alex Bateman

  60 shared

• Matthew G. Sampson

  Duke University

  54 shared

• Fred P. Davis

  Celsius Therapeutics (United States)

  52 shared

• John R. Sedor

  48 shared

• Laura Mariani

  University of Colorado Denver

  48 shared

• Jaina Mistry

  Cambridge University Hospitals NHS Foundation Trust

  41 shared

Labs

• Eddy LabPI

  Not provided

Education

• Ph.D., Molecular, Cellular, and Developmental Biology

  University of Colorado Boulder

  1991

• BS, Biology

  California Institute of Technology

  1986