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From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age(More)
MOTIVATION This article extends our recent research on penalized estimation methods in genome-wide association studies to the realm of rare variants. RESULTS The new strategy is tested on both simulated and real data. Our findings on breast cancer data replicate previous results and shed light on variant effects within genes. AVAILABILITY Rare variant(More)
Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health(More)
Cancer stem cells represent a novel therapeutic target. The major challenge in targeting leukemic stem cells (LSC) is finding therapies that largely spare normal hematopoietic stem cells (HSC) while eradicating quiescent LSCs. We present a mathematical model to predict how selective a therapy must be to ensure that enough HSCs survive when LSCs have been(More)
PURPOSE DNA damage recognition and repair play a major role in risk for breast cancer. We investigated 104 single nucleotide polymorphisms (SNP) in 17 genes whose protein products are involved in double-stranded break repair (DSBR). EXPERIMENTAL DESIGN We used a case-control design. Both the case individuals affected with breast cancer or with both breast(More)
Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death(More)
MOTIVATION Biological networks are often modeled by random graphs. A better modeling vehicle is a multigraph where each pair of nodes is connected by a Poisson number of edges. In the current model, the mean number of edges equals the product of two propensities, one for each node. In this context it is possible to construct a simple and effective algorithm(More)
Whole exome and whole genome sequencing are likely to be potent tools in the study of common diseases and complex traits. Despite this promise, some very difficult issues in data management and statistical analysis must be squarely faced. The number of rare variants identified by sequencing is apt to be much larger than the number of common variants(More)
Stochastic simulation methods are important in modeling chemical reactions, and biological and physical stochastic processes describable as continuous-time discrete-state Markov chains with a finite number of reactant species and reactions. The current algorithm of choice, tau-leaping, achieves fast and accurate stochastic simulation by taking large time(More)
The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down(More)