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A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals.

Chen J, Rozowsky J, Galeev TR, Harmanci A, Kitchen R, Bedford J, Abyzov A, Kong Y, Regan L, Gerstein M - Nat Commun (2016)

Bottom Line: Here, we provide insights into the functional effect of these variants using allele-specific behaviour.Since many allelic variants are rare, aggregation across multiple individuals is necessary to identify broadly applicable 'allelic elements'.Our results serve as an allele-specific annotation for the 1000 Genomes variant catalogue and are distributed as an online resource (alleledb.gersteinlab.org).

View Article: PubMed Central - PubMed

Affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.

ABSTRACT
Large-scale sequencing in the 1000 Genomes Project has revealed multitudes of single nucleotide variants (SNVs). Here, we provide insights into the functional effect of these variants using allele-specific behaviour. This can be assessed for an individual by mapping ChIP-seq and RNA-seq reads to a personal genome, and then measuring 'allelic imbalances' between the numbers of reads mapped to the paternal and maternal chromosomes. We annotate variants associated with allele-specific binding and expression in 382 individuals by uniformly processing 1,263 functional genomics data sets, developing approaches to reduce the heterogeneity between data sets due to overdispersion and mapping bias. Since many allelic variants are rare, aggregation across multiple individuals is necessary to identify broadly applicable 'allelic elements'. We also found SNVs for which we can anticipate allelic imbalance from the disruption of a binding motif. Our results serve as an allele-specific annotation for the 1000 Genomes variant catalogue and are distributed as an online resource (alleledb.gersteinlab.org).

No MeSH data available.


Related in: MedlinePlus

Inheritance of allele-specific behaviour.(a) The left panel shows plots for the TF CTCF (top row) and ASE (bottom row) being examined for inheritance in the CEU trio (Father: NA12891, blue; Mother: NA12892, red; Child: NA12878, green). Each point on the plot represents the allelic ratio of a common ASB SNV between the parent (x-axis) and the child (y-axis), by computing the proportion of reads mapping to the reference allele at that SNV. High Pearson's correlations, r, observed in both parent-child comparisons for CTCF (r≥0.78) signify strong heritability in allele-specific behaviour. ASE also shows considerably strong evidence of heritability but has comparatively lower r values. (b) The bar plot at the top right panel presents the r values for ASB in two TFs and ASE in our analyses.
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f4: Inheritance of allele-specific behaviour.(a) The left panel shows plots for the TF CTCF (top row) and ASE (bottom row) being examined for inheritance in the CEU trio (Father: NA12891, blue; Mother: NA12892, red; Child: NA12878, green). Each point on the plot represents the allelic ratio of a common ASB SNV between the parent (x-axis) and the child (y-axis), by computing the proportion of reads mapping to the reference allele at that SNV. High Pearson's correlations, r, observed in both parent-child comparisons for CTCF (r≥0.78) signify strong heritability in allele-specific behaviour. ASE also shows considerably strong evidence of heritability but has comparatively lower r values. (b) The bar plot at the top right panel presents the r values for ASB in two TFs and ASE in our analyses.

Mentions: The CEU trio is a well-studied family and with multiple ChIP-seq studies performed on different TFs. Previous studies have also presented allele-specific inheritance91419. Here, after uniformly processing data sets from multiple studies, we are able to analyse and compare the heritability of ASE and ASB across two DNA-binding proteins in a consistent manner (Fig. 4; see the ‘Methods' section). For the DNA-binding protein CTCF and PU.1 (also SPI1, or spleen focus forming virus proviral integration proto-oncogene), we observed a high parent–child correlation (Fig. 4, Supplementary Table 4), denoting great similarity in allelic directionality (Pearson's correlation, r≥0.78 in both parent–child plots). We also observed considerable heritability in ASE, but to a lesser degree. In general, the high inheritance of allele-specific SNVs observed in the same allelic direction from parent to child also implies a sequence dependency in allele-specific behaviour.


A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals.

Chen J, Rozowsky J, Galeev TR, Harmanci A, Kitchen R, Bedford J, Abyzov A, Kong Y, Regan L, Gerstein M - Nat Commun (2016)

Inheritance of allele-specific behaviour.(a) The left panel shows plots for the TF CTCF (top row) and ASE (bottom row) being examined for inheritance in the CEU trio (Father: NA12891, blue; Mother: NA12892, red; Child: NA12878, green). Each point on the plot represents the allelic ratio of a common ASB SNV between the parent (x-axis) and the child (y-axis), by computing the proportion of reads mapping to the reference allele at that SNV. High Pearson's correlations, r, observed in both parent-child comparisons for CTCF (r≥0.78) signify strong heritability in allele-specific behaviour. ASE also shows considerably strong evidence of heritability but has comparatively lower r values. (b) The bar plot at the top right panel presents the r values for ASB in two TFs and ASE in our analyses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837449&req=5

f4: Inheritance of allele-specific behaviour.(a) The left panel shows plots for the TF CTCF (top row) and ASE (bottom row) being examined for inheritance in the CEU trio (Father: NA12891, blue; Mother: NA12892, red; Child: NA12878, green). Each point on the plot represents the allelic ratio of a common ASB SNV between the parent (x-axis) and the child (y-axis), by computing the proportion of reads mapping to the reference allele at that SNV. High Pearson's correlations, r, observed in both parent-child comparisons for CTCF (r≥0.78) signify strong heritability in allele-specific behaviour. ASE also shows considerably strong evidence of heritability but has comparatively lower r values. (b) The bar plot at the top right panel presents the r values for ASB in two TFs and ASE in our analyses.
Mentions: The CEU trio is a well-studied family and with multiple ChIP-seq studies performed on different TFs. Previous studies have also presented allele-specific inheritance91419. Here, after uniformly processing data sets from multiple studies, we are able to analyse and compare the heritability of ASE and ASB across two DNA-binding proteins in a consistent manner (Fig. 4; see the ‘Methods' section). For the DNA-binding protein CTCF and PU.1 (also SPI1, or spleen focus forming virus proviral integration proto-oncogene), we observed a high parent–child correlation (Fig. 4, Supplementary Table 4), denoting great similarity in allelic directionality (Pearson's correlation, r≥0.78 in both parent–child plots). We also observed considerable heritability in ASE, but to a lesser degree. In general, the high inheritance of allele-specific SNVs observed in the same allelic direction from parent to child also implies a sequence dependency in allele-specific behaviour.

Bottom Line: Here, we provide insights into the functional effect of these variants using allele-specific behaviour.Since many allelic variants are rare, aggregation across multiple individuals is necessary to identify broadly applicable 'allelic elements'.Our results serve as an allele-specific annotation for the 1000 Genomes variant catalogue and are distributed as an online resource (alleledb.gersteinlab.org).

View Article: PubMed Central - PubMed

Affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.

ABSTRACT
Large-scale sequencing in the 1000 Genomes Project has revealed multitudes of single nucleotide variants (SNVs). Here, we provide insights into the functional effect of these variants using allele-specific behaviour. This can be assessed for an individual by mapping ChIP-seq and RNA-seq reads to a personal genome, and then measuring 'allelic imbalances' between the numbers of reads mapped to the paternal and maternal chromosomes. We annotate variants associated with allele-specific binding and expression in 382 individuals by uniformly processing 1,263 functional genomics data sets, developing approaches to reduce the heterogeneity between data sets due to overdispersion and mapping bias. Since many allelic variants are rare, aggregation across multiple individuals is necessary to identify broadly applicable 'allelic elements'. We also found SNVs for which we can anticipate allelic imbalance from the disruption of a binding motif. Our results serve as an allele-specific annotation for the 1000 Genomes variant catalogue and are distributed as an online resource (alleledb.gersteinlab.org).

No MeSH data available.


Related in: MedlinePlus