Extensions of Laplacian Eigenmaps for Manifold Learning

This thesis deals with the theory and practice of manifold learning, especially as they relate to the problem of classification. We begin with a well known algorithm, Laplacian Eigenmaps, and then proceed to extend it in two independent directions. First, we generalize this algorithm to allow for the use of partially labeled data, and establish the theoretical foundation of the resulting semi-supervised learning method. Second, we consider two ways of accelerating the most computationally intensive step of Laplacian Eigenmaps, the construction of an adjacency graph. Both of them produce high quality approximations, and we conclude by showing that they work well together to achieve a dramatic reduction in computational time

Associations of autozygosity with a broad range of human phenotypes

Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding