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Lai, E.

Publications and source records attributed to Lai, E..

2 recordsLinked to original sources

Crossbrowse: A versatile genome browser for visualizing comparative experimental data

The recent beyond-exponential growth in diverse collections of deep sequencing datasets creates enormous opportunities for discovery, concomitant with new challenges for displaying and interpreting these data. Notably, the availability of scores of whole genome sequences in multiple species clades enables comparative studies of functional elements. However, current genome browsers do not permit effective visualization of multigenome experimental data. Here, we present CrossBrowse, a standalone desktop application for displaying and browsing cross-species genomic datasets. We utilize data standards and graphic representation of popular browsers, and incorporate an intuitive graphical visualization of genome synteny that facilitates and drives human interrogation of comparative data. Our platform permits users with minimal informatics capacity to select arbitrary sets of genomes for display, upload and configure multiple datasets, and interact with vertebrate-sized genomic datasets in real-time. We illustrate the utility of CrossBrowse with interrogation of comparative invertebrate and mammalian datasets that provide insights into diverse aspects of transcriptional and post-transcriptional regulation. Of note, we show examplars of both preservation and divergence of functional elements that cannot be inferred from sequence alignments alone. Moreover, we demonstrate how inspection of primary data using CrossBrowse exposes an artifact in a typical strategy for assigning species-specific functional elements, and drives the implementation of an improved computational strategy. We anticipate that CrossBrowse will greatly foster user-based discovery within multispecies genomic datasets, and inform their bioinformatic interpretation.

bioinformatics

Deep experimental profiling of microRNA diversity, deployment, and evolution across the Drosophila genus

Comparative genomic analyses of microRNAs (miRNAs) have yielded myriad insights into their biogenesis and regulatory activity. While miRNAs have been deeply annotated in a small cohort of model organisms, evolutionary assessments of miRNA flux are clouded by the functional uncertainty of orthologs in related species, and insufficient data regarding the extent of species-specific miRNAs. We address this by generating a comparative small RNA (sRNA) catalog of unprecedented breadth and depth across the Drosophila genus, extending our extant deep analyses of D. melanogaster with sRNA data from multiple tissues of 11 other fly species. Aggregate analysis of several billion sRNA reads permits curation of accurate and holistic compendia of miRNAs across this genus, providing abundant opportunities to identify species- and clade-specific variation in miRNA identity, abundance, and processing. Amongst well-conserved miRNAs, we observe unexpected cases of clade-specific variation in 5' end precision, occasional antisense loci, and some putatively non-canonical loci. We also employ strict criteria to identify a massive set (649) of novel, evolutionarily-restricted miRNAs. Amongst the bulk collection of species-restricted miRNAs, two notable subpopulations of rapidly-evolving miRNAs are splicing-derived mirtrons and testis-restricted, clustered (TRC) canonical miRNAs. We quantify rates of miRNA birth and death using our annotation and a phylogenetic model for estimating rates of miRNA turnover in the presence of annotation uncertainty. We show striking differences in birth and death rates across miRNA classes defined by biogenesis pathway, genomic clustering, and tissue restriction, and even identify variation heterogeneity amongst Drosophila clades. In particular, distinct molecular rationales underlie the distinct evolutionary behavior of different miRNA classes. We broaden observations made from D. melanogaster as Drosophilid-wide principles for opposing evolutionary viewpoints for miRNA maintenance. Mirtrons are associated with a high rate of 3' untemplated addition, a mechanism that impedes their biogenesis, whereas TRC miRNAs appear to evolve under positive selection. Altogether, these data reveal miRNA diversity amongst Drosophila species and permit future discoveries in understanding their emergence and evolution.

genomics