Michael J. Italia

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Universal trees of life based on small-subunit (SSU) ribosomal RNA (rRNA) support the separate mono/holophyly of the domains Archaea (archaebacteria), Bacteria (eubacteria) and Eucarya (eukaryotes) and the placement of extreme thermophiles at the base of the Bacteria. The concept of universal tree reconstruction recently has been upset by protein trees that(More)
Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent-offspring trios. CHD cases(More)
Horizontal gene transfer (HGT) has long been recognized as a principal force in the evolution of genomes. Genome sequences of Archaea and Bacteria have revealed the existence of genes whose similarity to loci in distantly related organisms is explained most parsimoniously by HGT events. In most multicellular organisms, such genetic fixation can occur only(More)
We have developed a method for the prediction of an amino acid sequence that is compatible with a three-dimensional backbone structure. Using only a backbone structure of a protein as input, the algorithm is capable of designing sequences that closely resemble natural members of the protein family to which the template structure belongs. In general, the(More)
RATIONALE Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism arrays and whole(More)
With genome-wide cancer studies producing large DNA sequence data sets, novel computational approaches toward better understanding the role of mutations in tumor survival and proliferation are greatly needed. Tumors are widely viewed to be influenced by Darwinian processes, yet molecular evolutionary analysis, invaluable in other DNA sequence studies, has(More)
Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen Streptococcus pneumoniae. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral(More)
The efficacy of beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs), however, this has been less so for amoxicillin than for penicillin. Recently, there have been a number of important methods developed to detect molecular adaptation in protein coding genes. The(More)
Biomedical researchers share a common challenge of making complex data understandable and accessible as they seek inherent relationships between attributes in disparate data types. Data discovery in this context is limited by a lack of query systems that efficiently show relationships between individual variables, but without the need to navigate underlying(More)
Biomedical researchers share a common challenge of making complex data understandable and accessible. This need is increasingly acute as investigators seek opportunities for discovery amidst an exponential growth in the volume and complexity of laboratory and clinical data. To address this need, we developed Harvest, an open source framework that provides a(More)
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