Adriana Arneson

San Diego, California, United States Contact Info
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  • Protillion Biosciences

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Publications

  • ConsHMM Atlas: conservation state annotations for major genomes and human genetic variation

    NAR Genomics and Bioinformatics

    ConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here, we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments…

    ConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here, we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments. Additionally, we extend ConsHMM to generate allele-specific annotations, which we use to produce conservation state annotations for every possible single-nucleotide mutation in the human genome. Finally, we provide a web interface to interactively visualize parameters and annotation enrichments for ConsHMM models. These annotations and visualizations comprise the ConsHMM Atlas, which we expect will be a valuable resource for analyzing a variety of major genomes and genetic variation.

    Other authors
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  • Systematic discovery of conservation states for single-nucleotide annotation of the human genome

    Communications Biology

    Comparative genomics sequence data is an important source of information for interpreting genomes. Genome-wide annotations based on this data have largely focused on univariate scores or binary elements of evolutionary constraint. Here we present a complementary whole genome annotation approach, ConsHMM, which applies a multivariate hidden Markov model to learn de novo ‘conservation states’ based on the combinatorial and spatial patterns of which species align to and match a reference genome in…

    Comparative genomics sequence data is an important source of information for interpreting genomes. Genome-wide annotations based on this data have largely focused on univariate scores or binary elements of evolutionary constraint. Here we present a complementary whole genome annotation approach, ConsHMM, which applies a multivariate hidden Markov model to learn de novo ‘conservation states’ based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multiple species DNA sequence alignment. We applied ConsHMM to a 100-way vertebrate sequence alignment to annotate the human genome at single nucleotide resolution into 100 conservation states. These states have distinct enrichments for other genomic information including gene annotations, chromatin states, repeat families, and bases prioritized by various variant prioritization scores. Constrained elements have distinct heritability partitioning enrichments depending on their conservation state assignment. ConsHMM conservation states are a resource for analyzing genomes and genetic variants.

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  • Professor Ahmet Ay and students merge biology, math, and computer science in published papers

    Colgate University

    Other authors
    • Kellyann Hayes
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  • Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves

    Development

    The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations…

    The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations have been proposed, the mechanism underlying traveling waves has remained elusive. Here, we combined molecular-level computational modeling and quantitative experimentation to solve this puzzle. Our model predicts the existence of an increasing gradient of gene expression time delays along the posterior to anterior direction to recapitulate spatiotemporal profiles of the traveling segmentation clock waves in different genetic backgrounds in zebrafish. We validated this prediction by measuring an increased time delay of oscillatory Her1 protein production along the unsegmented tissue. Our results refuted the need for spatial expansion of the core feedback loop to explain the occurrence of traveling waves. Spatial regulation of gene expression time delays is a novel way of creating dynamic patterns; this is the first report demonstrating such a control mechanism in any tissue and future investigations will explore the presence of analogous examples in other biological systems.

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  • Short-lived Her proteins drive robust synchronized oscillations in the zebrafish segmentation clock

    Development

    Oscillations are prevalent in natural systems. A gene expression oscillator, called the segmentation clock, controls segmentation of precursors of the vertebral column. Genes belonging to the Hes/her family encode the only conserved oscillating genes in all analyzed vertebrate species. Hes/Her proteins form dimers and negatively autoregulate their own transcription. Here, we developed a stochastic two-dimensional multicellular computational model to elucidate how the dynamics, i.e. period…

    Oscillations are prevalent in natural systems. A gene expression oscillator, called the segmentation clock, controls segmentation of precursors of the vertebral column. Genes belonging to the Hes/her family encode the only conserved oscillating genes in all analyzed vertebrate species. Hes/Her proteins form dimers and negatively autoregulate their own transcription. Here, we developed a stochastic two-dimensional multicellular computational model to elucidate how the dynamics, i.e. period, amplitude and synchronization, of the segmentation clock are regulated. We performed parameter searches to demonstrate that autoregulatory negative-feedback loops of the redundant repressor Her dimers can generate synchronized gene expression oscillations in wild-type embryos and reproduce the dynamics of the segmentation oscillator in different mutant conditions. Our model also predicts that synchronized oscillations can be robustly generated as long as the half-lives of the repressor dimers are shorter than 6 minutes. We validated this prediction by measuring, for the first time, the half-life of Her7 protein as 3.5 minutes. These results demonstrate the importance of building biologically realistic stochastic models to test biological models more stringently and make predictions for future experimental studies.

    Other authors
    • Ahmet Ay
    • Jack Holland
    • Stephan Knierer
    • Ertugrul Ozbudak
    See publication

Patents

Languages

  • Romanian

    Native or bilingual proficiency

  • Spanish

    Limited working proficiency

  • Russian

    Elementary proficiency

  • French

    Elementary proficiency

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