Institution
Texas Medical Center
Healthcare•Houston, Texas, United States•
About: Texas Medical Center is a healthcare organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Stroke. The organization has 2845 authors who have published 2394 publications receiving 79426 citations.
Topics: Population, Stroke, Cancer, Transplantation, Gene
Papers published on a yearly basis
Papers
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TL;DR: This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods and demonstrated the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing, which is the first genome sequenced by next-generation technologies.
Abstract: Next-generation sequencing technologies are revolutionizing human genomics, promising to yield draft genomes cheaply and quickly. One such technology has now been used to analyse much of the genetic code of a single individual — who happens to be James D. Watson. The procedure, which involves no cloning of the genomic DNA, makes use of the latest 454 parallel sequencing instrument. The sequence cost less than US$1 million (and a mere two months) to produce, compared to the approximately US$100 million reported for sequencing Craig Venter's genome by traditional methods. Still a major undertaking, but another step towards the goal of 'personalized genomes' and 'personalized medicine'. The DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels is reported. The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of ‘genomic medicine’. However, the formidable size of the diploid human genome1, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2–40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual2 by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of ‘personalized genome sequencing’.
1,879 citations
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TL;DR: The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals.
1,150 citations
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TL;DR: Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.
Abstract: ContextThe direct thrombin inhibitor bivalirudin has been associated with better
efficacy and less bleeding than heparin during coronary balloon angioplasty
but has not been widely tested during contemporary percutaneous coronary intervention
(PCI).ObjectiveTo determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa
(Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI,
compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection
from periprocedural ischemic and hemorrhagic complications.Design, Setting, and ParticipantsThe Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical
Events (REPLACE)–2 trial, a randomized, double-blind, active-controlled
trial conducted among 6010 patients undergoing urgent or elective PCI at 233
community or referral hospitals in 9 countries from October 2001 through August
2002.InterventionsPatients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg
bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional
Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned
Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups
received daily aspirin and a thienopyridine for at least 30 days after PCI.Main Outcome MeasuresThe primary composite end point was 30-day incidence of death, myocardial
infarction, urgent repeat revascularization, or in-hospital major bleeding;
the secondary composite end point was 30-day incidence of death, myocardial
infarction, or urgent repeat revascularization.ResultsProvisional Gp IIb/IIIa blockade was administered to 7.2% of patients
in the bivalirudin group. By 30 days, the primary composite end point had
occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients
in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval,
0.77-1.09; P = .32). The secondary composite end
point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients
in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval
0.90-1.32; P = .40). Prespecified statistical criteria
for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end
points. In-hospital major bleeding rates were significantly reduced by bivalirudin
(2.4% vs 4.1%; P<.001).ConclusionsBivalirudin with provisional Gp IIb/IIIa blockade is statistically not
inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary
PCI with regard to suppression of acute ischemic end points and is associated
with less bleeding.
1,148 citations
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TL;DR: The discovery of submicroscopic copy-number variations (CNVs) present in the authors' genomes has changed dramatically their perspective on DNA structural variation and disease and it is now thought that CNVs encompass more total nucleotides and arise more frequently than SNPs.
Abstract: During the last quarter of the twentieth century, our knowledge about human genetic variation was limited mainly to the heterochromatin polymorphisms, large enough to be visible in the light microscope, and the single nucleotide polymorphisms (SNPs) identified by traditional PCR-based DNA sequencing. In the past five years, the rapid development and expanded use of microarray technologies, including oligonucleotide array comparative genomic hybridization and SNP genotyping arrays, as well as next-generation sequencing with “paired-end” methods, has enabled a whole-genome analysis with essentially unlimited resolution. The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA structural variation and disease. It is now thought that CNVs encompass more total nucleotides and arise more frequently than SNPs. CNVs, to a larger extent than SNPs, have been shown to be responsible for human evolution, genetic diversity between individuals,...
1,121 citations
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TL;DR: Copy number variation, especially gene duplication and exon shuffling, can be a predominant mechanism driving gene and genome evolution and appear much higher for CNVs than for SNPs.
Abstract: Copy number variation (CNV) is a source of genetic diversity in humans. Numerous CNVs are being identified with various genome analysis platforms, including array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) genotyping platforms, and next-generation sequencing. CNV formation occurs by both recombination-based and replication-based mechanisms and de novo locus-specific mutation rates appear much higher for CNVs than for SNPs. By various molecular mechanisms, including gene dosage, gene disruption, gene fusion, position effects, etc., CNVs can cause Mendelian or sporadic traits, or be associated with complex diseases. However, CNV can also represent benign polymorphic variants. CNVs, especially gene duplication and exon shuffling, can be a predominant mechanism driving gene and genome evolution.
1,100 citations
Authors
Showing all 2878 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eric N. Olson | 206 | 814 | 144586 |
Scott M. Grundy | 187 | 841 | 231821 |
Joseph Jankovic | 153 | 1146 | 93840 |
Geoffrey Burnstock | 141 | 1488 | 99525 |
George Perry | 139 | 923 | 77721 |
David Y. Graham | 138 | 1047 | 80886 |
James R. Lupski | 136 | 844 | 74256 |
Savio L. C. Woo | 135 | 785 | 62270 |
Henry T. Lynch | 133 | 925 | 86270 |
Joseph P. Broderick | 130 | 504 | 72779 |
Huda Y. Zoghbi | 127 | 463 | 65169 |
Paul M. Vanhoutte | 127 | 868 | 62177 |
Meletios A. Dimopoulos | 122 | 1371 | 71871 |
John B. Holcomb | 120 | 733 | 53760 |
John S. Mattick | 116 | 367 | 64315 |