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We describe factored spectrally transformed linear mixed models (FaST-LMM), an algorithm for genome-wide association studies (GWAS) that scales linearly with cohort size in both run time and memory use. On Wellcome Trust data for 15,000 individuals, FaST-LMM ran an order of magnitude faster than current efficient algorithms. Our algorithm can analyze data(More)
MOTIVATION Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these(More)
MOTIVATION Set-based variance component tests have been identified as a way to increase power in association studies by aggregating weak individual effects. However, the choice of test statistic has been largely ignored even though it may play an important role in obtaining optimal power. We compared a standard statistical test-a score test-with a recently(More)
Multiple realizations of continuous-valued time series from a stochastic process often contain systematic variations in rate and amplitude. To leverage the information contained in such noisy replicate sets, we need to align them in an appropriate way (for example, to allow the data to be properly combined by adaptive averaging). We present the Continuous(More)
It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and(More)
In many application domains, such as computational biology, the goal of graphical model structure learning is to uncover discrete relationships between entities. For example, in our problem of interest concerning HIV vaccine design , we want to infer which HIV peptides interact with which immune system molecules (HLA molecules). For problems of this nature,(More)
We present a model for predicting HLA class I restricted CTL epitopes. In contrast to almost all other work in this area, we train a single model on epitopes from all HLA alleles and supertypes, yet retain the ability to make epitope predictions for specific HLA alleles. We are therefore able to leverage data across all HLA alleles and/or their supertypes,(More)
In epigenome-wide association studies, cell-type composition often differs between cases and controls, yielding associations that simply tag cell type rather than reveal fundamental biology. Current solutions require actual or estimated cell-type composition--information not easily obtainable for many samples of interest. We propose a method,(More)
The combined method of LC-MS/MS is increasingly being used to explore differences in the proteomic composition of complex biological systems. The reliability and utility of such comparative protein expression profiling studies is critically dependent on an accurate and rigorous assessment of quantitative changes in the relative abundance of the myriad of(More)
Hereditary predisposition and causative environmental exposures have long been recognized in human malignancies. In most instances, cancer cases occur sporadically, suggesting that environmental influences are critical in determining cancer risk. To test the influence of genetic polymorphisms on breast cancer risk, we have measured 98 single nucleotide(More)