Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Data Mining Practical Machine Learning Tools and Techniques

Demand has never been greater for revolutionary technologies that deliver fast, inexpensive and accurate genome information. This challenge has catalysed the development of next-generation sequencing (NGS) technologies. The inexpensive production of large volumes of sequence data is the primary advantage over conventional methods. Here, I present a technical review of template preparation, sequencing and imaging, genome alignment and assembly approaches, and recent advances in current and near-term commercially available NGS instruments. I also outline the broad range of applications for NGS technologies, in addition to providing guidelines for platform selection to address biological questions of interest.

/pdf/sequencing-technologies-the-next-generation-599pyrfdla.pdf

Sequencing technologies-the next generation

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Modern Applied Statistics With S

Methods for characterizing patients diagnosed with histaminergic diseases are described. Nucleic acid molecules that include a histamine-N-methyltransferase intron variant sequence associated with a histaminergic disease also are described.

Histamine-N-methyltransferase variants associated with histaminergic disease

Study of Meditation and Blood Pressure

Materials and methods for evaluating cellular responses to acetaminophen and assessing susceptibility to liver damage.

Biomarkers for acetaminophen toxicity

BACKGROUND
Cardiac toxicity is a serious complication of HER2-directed therapies and anthracyclines. HER2 codon 655 and SLC28A3 gene polymorphisms have been reported to be associated with cardiac toxicity from anti-HER2 and anthracycline therapy, respectively. Association of the polymorphism at HER2 codon 655 with prognosis has also been reported.


METHODS
Whole blood samples from patients treated on a randomized adjuvant breast cancer trial (BCIRG-006) that compared anthracycline-based chemotherapy to trastuzumab plus either anthracycline or non-anthracycline chemotherapy were tested for genetic polymorphisms in HER2 codon 655 and SLC28A3 Genotypes were correlated with cardiac function and disease-free survival (DFS) outcomes.


RESULTS
Of 3,222 patients enrolled in BCIRG-006, 662 patient samples were successfully genotyped for the rs1136201 allele in HER2 (codon 655): 424 (64%) were AA, 30 (4.5%) were GG, and 208 (31%) were AG genotype. Additionally, 665 patient samples were successfully genotyped for the rs7853758 allele in the SLC28A3 gene: 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG genotype. Follow up time was 10 years. No correlation between DFS, cardiac event rate or mean left ventricular ejection fraction (LVEF) and rs1136201 genotype was seen in the trastuzumab treated or non-trastuzumab treated patients. Moreover, mean LVEF and cardiac event rates were similar in all rs7853758 genotype groups treated with anthracycline-based therapy.


CONCLUSIONS
In the largest study to date to evaluate whether two polymorphisms are associated with DFS and/or cardiac toxicity in HER2 positive breast cancer treated with trastuzumab and/or anthracyclines, we observed no correlation.

Richard M. Weinshilboum

Papers

Histamine-N-methyltransferase variants associated with histaminergic disease

Study of Meditation and Blood Pressure

Biomarkers for acetaminophen toxicity

Genetic polymorphisms and correlation with treatment induced cardiotoxicity and prognosis in breast cancer patients.

Human platelet phenol sulfotransferase (PST): Individual variations in the thermal stability of the 'TS' or 'P' form