Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test
© 2016 The Author(s).We present a novel approach to detect potential cis-acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against...
| Main Authors: | , , , , |
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| Format: | Conference Paper |
| Published: |
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/52638 |
| _version_ | 1848758975976177664 |
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| author | Peralta, J. Almeida, M. Abraham, L. Moses, Eric Blangero, J. |
| author_facet | Peralta, J. Almeida, M. Abraham, L. Moses, Eric Blangero, J. |
| author_sort | Peralta, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2016 The Author(s).We present a novel approach to detect potential cis-acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against expression phenotypes. To test our method we used public ENCODE whole genome DNase-I sequencing data, from a single sample, to estimate the functional potentials of the subset of 10,552 noncoding heterozygous single-nucleotide polymorphisms (SNPs) that were also present in the Genetic Analysis Workshop 19 (GAW19) family-based data set. We then built two covariance kernels, one nonweighted and one weighted by the functional potentials, and conducted kernel-based variance component association analyses against the 20,527 transcript expression phenotypes in the GAW19 family-based data set. We found signals of potential cis-regulatory effects, that surpassed the Bonferroni significance threshold, for ten transcripts. Stepwise removal of the cis-located SNPs from the weighted kernel lead to the disappearance of the association signal from our top transcript hit. We found compelling evidence of allele-specific cis-regulation for four transcripts using both kernels, and our results agree with previous research that suggests the involvement of specific cis-located variants in the regulation of their neighboring gene. |
| first_indexed | 2025-11-14T09:52:32Z |
| format | Conference Paper |
| id | curtin-20.500.11937-52638 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:52:32Z |
| publishDate | 2016 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-526382017-09-13T15:39:24Z Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test Peralta, J. Almeida, M. Abraham, L. Moses, Eric Blangero, J. © 2016 The Author(s).We present a novel approach to detect potential cis-acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against expression phenotypes. To test our method we used public ENCODE whole genome DNase-I sequencing data, from a single sample, to estimate the functional potentials of the subset of 10,552 noncoding heterozygous single-nucleotide polymorphisms (SNPs) that were also present in the Genetic Analysis Workshop 19 (GAW19) family-based data set. We then built two covariance kernels, one nonweighted and one weighted by the functional potentials, and conducted kernel-based variance component association analyses against the 20,527 transcript expression phenotypes in the GAW19 family-based data set. We found signals of potential cis-regulatory effects, that surpassed the Bonferroni significance threshold, for ten transcripts. Stepwise removal of the cis-located SNPs from the weighted kernel lead to the disappearance of the association signal from our top transcript hit. We found compelling evidence of allele-specific cis-regulation for four transcripts using both kernels, and our results agree with previous research that suggests the involvement of specific cis-located variants in the regulation of their neighboring gene. 2016 Conference Paper http://hdl.handle.net/20.500.11937/52638 10.1186/s12919-016-0013-1 unknown |
| spellingShingle | Peralta, J. Almeida, M. Abraham, L. Moses, Eric Blangero, J. Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title | Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title_full | Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title_fullStr | Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title_full_unstemmed | Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title_short | Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| title_sort | finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test |
| url | http://hdl.handle.net/20.500.11937/52638 |