Category: Publications
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You cannot tell a book by looking at the cover: Cryptic complexity in bacterial evolution
Abstract: Do genetically closely related organisms under identical, but strong selection pressure converge to a common resistant genotype or will they diverge to different genomic solutions? This question gets at the heart of how rough is the fitness landscape in the local vicinity of two closely related strains under stress. We chose a Growth Advantage…
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Weddell seal foraging dives: comparison of free-ranging and isolated-hole paradigms
Weddell seals are polar predators that must partition their time between many behaviors, including hunting prey at depth and breathing at the surface. Although they have been well studied, little is known about how foraging behavior changes when access to breathing holes is restricted, such as in the isolated-hole paradigm. The current study took advantage…
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Guide to the UCSC Genome Browser
This tutorial is aimed at the biologist who is interested in exploring protein-coding genes using the University of California Santa Cruz (UCSC) Genome Browser. It is geared towards those who have little or no experience using the UCSC Genome Browser and for more advanced users who are not familiar with many of the gene-oriented browser…
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Molecular Pathways: Extracting Medical Knowledge from High Throughput Genomic Data.
Abstract: High-throughput genomic data that measures RNA expression, DNA copy number, mutation status, and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. Although the number of possible lesions is vast, different genomic alterations may result in concordant expression…
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“Function-first” lead discovery: mode of action profiling of natural product libraries using image-based screening.
Abstract: Cytological profiling is a high-content image-based screening technology that provides insight into the mode of action (MOA) for test compounds by directly measuring hundreds of phenotypic cellular features. We have extended this recently reported technology to the mechanistic characterization of unknown natural products libraries for the direct prediction of compound MOAs at the primary…
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The complete genome sequence of a Neanderthal from the Altai Mountains
We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships…
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Databases and Genome Browsers
The advent of the human genome project and subsequent projects to sequence genomes of other species and multiple individuals has driven the need for tools that can visualize vast amounts of genomics data. Software for genome browsing has had a vast impact in the arenas of human medical and genetics research, enabling researchers to process…
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The ontogeny of aerobic and diving capacity in the skeletal muscles of Weddell seals
Our objective was to determine the ontogenetic changes in the skeletal muscles of Weddell seals that transform a non-diving pup into an elite diving adult. Muscle biopsies were collected from pups, juveniles and adults and analyzed for changes in fiber type, mitochondrial density, myoglobin concentrations and aerobic, lipolytic and anaerobic enzyme activities. The fiber type…
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A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing
A complete mitochondrial (mt) genome sequence was reconstructed from a 38,000 year-old Neandertal individual with 8341 mtDNA sequences identified among 4.8 Gb of DNA generated from ∼0.3 g of bone. Analysis of the assembled sequence unequivocally establishes that the Neandertal mtDNA falls outside the variation of extant human mtDNAs, and allows an estimate of the…
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Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements
The human and mouse genomes share a number of long, perfectly conserved nucleotide sequences, termed ultraconserved elements1. Whereas these regions can act as transcriptional enhancers when upstream of genes, those within genes are less well understood. In particular, the function of ultraconserved elements that overlap alternatively spliced exons of genes encoding RNA-binding proteins is unknown.…
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Single-molecule analysis of DNA-protein complexes using nanopores
We present a method for rapid measurement of DNA-protein interactions using voltage-driven threading of single DNA molecules through a protein nanopore. Electrical force applied to individual ssDNA-exonuclease I complexes pulls the two molecules apart, while ion current probes the dissociation rate of the complex. Nanopore force spectroscopy (NFS) reveals energy barriers affecting complex dissociation. This…
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The cost of foraging by a marine predator, the Weddell seal Leptonychotes weddellii: pricing by the stroke
Foraging by mammals is a complex suite of behaviors that can entail high energetic costs associated with supporting basal metabolism, locomotion and the digestion of prey. To determine the contribution of these various costs in a free-ranging marine mammal, we measured the post-dive oxygen consumption of adult Weddell seals (N=9) performing foraging and non-foraging dives…