A spectral graph approach to discovering genetic ancestry

Lee, Ann B.; Luca, Diana; Roeder, Kathryn

doi:10.1214/09-aoas281

Cited by 29 publications

(39 citation statements)

References 34 publications

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“…Examples include the movement of animals in a group, such as "flocking" in birds, and the emergence of common languages in primitive societies (11,12). Another important application of the Laplacian is in spectral clustering, where it provides an efficient method for graph partitioning (13).…”

mentioning

confidence: 99%

Functional organization of the human 4D Nucleome

Chen

Muir

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.4D Nucleome | networks | Laplacian | interphase nucleus | phase plane

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mentioning

confidence: 99%

Functional organization of the human 4D Nucleome

Chen

Muir

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

110

150

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“…Existing publicly available collections of control data determine a common genetic ancestry space onto which cases and controls can be projected independently. GemTools [10,13,14] constructs ancestry spaces and performs such projections. The projected controls are then used to estimate the control minor allele frequency distribution (MAFD) over the ancestry space.…”

Section: Overview Of Unicornmentioning

confidence: 99%

“…Instead, our algorithm first discovers clusters of subjects with relatively homogeneous ancestry, which then require fewer eigenvectors to represent ancestry within a cluster. To achieve this purpose we use GemTools [13], a software tool based on a spectral graph approach [10] quite similar to PCA. We note, however, that many popular ancestry mapping techniques could be successfully paired with UNICORN in place of GemTools.…”

Section: Ancestry Mapping Via Gemtoolsmentioning

confidence: 99%

A method to exploit the structure of genetic ancestry space to enhance case-control studies

Bodea

Neale

Ripke

et al. 2016

Preprint

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One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in cases are contrasted with those from population-based samples used as controls. In an ideal world we would know population-level allele frequencies, releasing * Correspondence: roeder@andrew.cmu.edu 1 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/043166 doi: bioRxiv preprint first posted online Mar. 10, 2016; researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of controls from studies of Crohn's disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful and convenient genetic association analyses without access to the individual level data.

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“…More recent additions to this package include analysis or rare variants, including CNVs, and next-generation sequencing. Correction for population stratification is usually conducted in PLINK using multidimensional scaling (MDS) or by principal component analysis as implemented in other packages such as Spectral-GEM [75,76].…”

Section: Genome-wide Association Studiesmentioning

confidence: 99%