18,081 research outputs found
Non-stationary patterns of isolation-by-distance: inferring measures of local genetic differentiation with Bayesian kriging
Patterns of isolation-by-distance arise when population differentiation
increases with increasing geographic distances. Patterns of
isolation-by-distance are usually caused by local spatial dispersal, which
explains why differences of allele frequencies between populations accumulate
with distance. However, spatial variations of demographic parameters such as
migration rate or population density can generate non-stationary patterns of
isolation-by-distance where the rate at which genetic differentiation
accumulates varies across space. To characterize non-stationary patterns of
isolation-by-distance, we infer local genetic differentiation based on Bayesian
kriging. Local genetic differentiation for a sampled population is defined as
the average genetic differentiation between the sampled population and fictive
neighboring populations. To avoid defining populations in advance, the method
can also be applied at the scale of individuals making it relevant for
landscape genetics. Inference of local genetic differentiation relies on a
matrix of pairwise similarity or dissimilarity between populations or
individuals such as matrices of FST between pairs of populations. Simulation
studies show that maps of local genetic differentiation can reveal barriers to
gene flow but also other patterns such as continuous variations of gene flow
across habitat. The potential of the method is illustrated with 2 data sets:
genome-wide SNP data for human Swedish populations and AFLP markers for alpine
plant species. The software LocalDiff implementing the method is available at
http://membres-timc.imag.fr/Michael.Blum/LocalDiff.htmlComment: In press, Evolution 201
How to understand the cell by breaking it: network analysis of gene perturbation screens
Modern high-throughput gene perturbation screens are key technologies at the
forefront of genetic research. Combined with rich phenotypic descriptors they
enable researchers to observe detailed cellular reactions to experimental
perturbations on a genome-wide scale. This review surveys the current
state-of-the-art in analyzing perturbation screens from a network point of
view. We describe approaches to make the step from the parts list to the wiring
diagram by using phenotypes for network inference and integrating them with
complementary data sources. The first part of the review describes methods to
analyze one- or low-dimensional phenotypes like viability or reporter activity;
the second part concentrates on high-dimensional phenotypes showing global
changes in cell morphology, transcriptome or proteome.Comment: Review based on ISMB 2009 tutorial; after two rounds of revisio
The Kernel Interaction Trick: Fast Bayesian Discovery of Pairwise Interactions in High Dimensions
Discovering interaction effects on a response of interest is a fundamental
problem faced in biology, medicine, economics, and many other scientific
disciplines. In theory, Bayesian methods for discovering pairwise interactions
enjoy many benefits such as coherent uncertainty quantification, the ability to
incorporate background knowledge, and desirable shrinkage properties. In
practice, however, Bayesian methods are often computationally intractable for
even moderate-dimensional problems. Our key insight is that many hierarchical
models of practical interest admit a particular Gaussian process (GP)
representation; the GP allows us to capture the posterior with a vector of O(p)
kernel hyper-parameters rather than O(p^2) interactions and main effects. With
the implicit representation, we can run Markov chain Monte Carlo (MCMC) over
model hyper-parameters in time and memory linear in p per iteration. We focus
on sparsity-inducing models and show on datasets with a variety of covariate
behaviors that our method: (1) reduces runtime by orders of magnitude over
naive applications of MCMC, (2) provides lower Type I and Type II error
relative to state-of-the-art LASSO-based approaches, and (3) offers improved
computational scaling in high dimensions relative to existing Bayesian and
LASSO-based approaches.Comment: Accepted at ICML 2019. 20 pages, 4 figures, 3 table
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