A Panel of rSNPs Demonstrating Allelic Asymmetry in Both ChIP-seq and RNA-seq Data and the Search for Their Phenotypic Outcomes through Analysis of DEGs
Abstract
:1. Introduction
2. Results
2.1. Workflow for rSNP Identification
2.1.1. General Description
2.1.2. Using GWAS and eQTLs to Define Cutoff Thresholds
2.1.3. Setting Predicted Probabilities from Logistic Regression
2.2. Characterization of the Resulting rSNP Panel
2.2.1. Search for rSNPs within Known TF Binding Motifs
2.2.2. Overlapping with GWAS Variants
2.2.3. Finding rSNPs in GTExeQTLCollection
2.3. Assessing eQTLs in Human Brain RNA-seq Dataset
3. Discussion
4. Materials and Methods
4.1. Human NGS Data
4.2. Open Access Resources
4.3. NGS Data Preprocessing
4.3.1. Quality Filtering
4.3.2. Genomic Alignment and SNP Calling
4.4. Assessing Allele-Specific Binding and Expression Events
4.5. Z-Test
4.6. Evaluation of Linked SNP Pairs by HAMMING Distance
4.7. Transcription Factor Motif Disruption Analysis
4.8. Differential Expression Analysis
4.9. Construction of Protein–Protein Interaction Networks and Functional Annotation
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Regression Coefficient | Std. Error | p-Value | Sign |
---|---|---|---|---|
|log2FC1| | −0.547335 | 0.009193 | <2 × 10−16 | *** |
|log2FC2| | −0.022103 | 0.008592 | 0.0101 | * |
|log2FC1/FC2| | −0.125600 | 0.010718 | <2 × 10−16 | *** |
Identified SNPs | n | Overlapping with All GTEX eQTLs, % | Overlapping withthe GTExeQTLs with p-Value < 0.1, % | Positions Contained in GWAS Catalog, % |
---|---|---|---|---|
Heterozygous SNPs | ~4.3 × 106 | 13 | 8 | 2.1 |
SNPs with ASB (p-value < 0.1) | 58,191 | 15 | 10 | 2.5 |
SNPs with ASE (p-value < 0.1) | 230,553 | 15 | 10 | 2.7 |
SNPs with both ASB and ASE (both p-values < 0.1) | 20,321 | 23 | 18 | 3.0 |
SNPs with both ASB and ASE (z-test p-values < 0.0005) | 14,898 | 23 | 18 | 3.1 |
SNPs selected by predicted probabilities, pp > 0.1929408 | 14,543 | 26 | 20 | 3.5 |
SNPs selected by log regression and z-score | 10,318 | 26 | 21 | 3.7 |
rs7289432 22chr:19171209 | cSNP (rs738904) 22chr:19179872 | Total Number of Genotypes in 1000 Genomes | ||
---|---|---|---|---|
CC | AC | AA | ||
AA | 1084 | 5 | 0 | 1089 |
AG | 9 | 1042 | 5 | 1056 |
GG | 0 | 7 | 352 | 359 |
Total number of genotypes in 1000 Genomes | 1093 | 1054 | 357 | 2504 |
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Korbolina, E.E.; Bryzgalov, L.O.; Ustrokhanova, D.Z.; Postovalov, S.N.; Poverin, D.V.; Damarov, I.S.; Merkulova, T.I. A Panel of rSNPs Demonstrating Allelic Asymmetry in Both ChIP-seq and RNA-seq Data and the Search for Their Phenotypic Outcomes through Analysis of DEGs. Int. J. Mol. Sci. 2021, 22, 7240. https://doi.org/10.3390/ijms22147240
Korbolina EE, Bryzgalov LO, Ustrokhanova DZ, Postovalov SN, Poverin DV, Damarov IS, Merkulova TI. A Panel of rSNPs Demonstrating Allelic Asymmetry in Both ChIP-seq and RNA-seq Data and the Search for Their Phenotypic Outcomes through Analysis of DEGs. International Journal of Molecular Sciences. 2021; 22(14):7240. https://doi.org/10.3390/ijms22147240
Chicago/Turabian StyleKorbolina, Elena E., Leonid O. Bryzgalov, Diana Z. Ustrokhanova, Sergey N. Postovalov, Dmitry V. Poverin, Igor S. Damarov, and Tatiana I. Merkulova. 2021. "A Panel of rSNPs Demonstrating Allelic Asymmetry in Both ChIP-seq and RNA-seq Data and the Search for Their Phenotypic Outcomes through Analysis of DEGs" International Journal of Molecular Sciences 22, no. 14: 7240. https://doi.org/10.3390/ijms22147240