Method for identifying aQTL regions whose genotype modulates transcription factor activity

1. A method of identifying one or more genetic determinants of transcription factor activity, comprising:

generating, using a computer processor, an inferred transcription factor activity profile using a nucleotide sequence-specific mathematical model of gene expression regulation; and

performing genetic analysis to identify at least one genetic determinant linked to a specific transcription factor segregant using said inferred transcription factor activity profile.

2. The method of claim 1 , wherein an allelic variation in said one or more genetic determinants modulates the transcription factor activity of said specific transcription factor.

3. The method of claim 1 , wherein generating an inferred transcription factor activity comprises:

obtaining a mRNA expression data set and a promoter affinity profile; and

generating said inferred transcription factor activity using said mRNA expression data set and said promoter affinity profile.

4. The method of claim 3 , wherein obtaining a promoter affinity profile comprises:

obtaining a position specific affinity matrix and a genomic sequence; and

generating a promoter affinity profile using said position specific affinity matrix and said genomic sequence.

5. The method of claim 4 , wherein obtaining a position specific affinity matrix comprises:

obtaining a position weight matrix; and

generating said position specific affinity matrix using said position weight matrix.

6. The method of claim 1 , wherein said genetic determinants comprise activity quantitative trait loci.

7. The method of claim 1 , wherein said genetic analysis is selected from the group consisting of genetic linkage analysis and association analysis.

8. The method of claim 7 , wherein said genetic analysis comprises genetic linkage analysis.

9. The method of claim 8 , wherein said activity quantitative trait loci are identified using a parametric t-test.

10. The method of claim 8 , wherein said activity quantitative trait loci are identified using a non-parametric Wilcoxon-Mann-Whitney test.

11. The method of claim 8 , wherein said activity quantitative trait loci are identified using composite interval mapping or another multiple locus genetic mapping algorithm.

12. The method of claim 1 , further comprising connecting said specific transcription factor to one or more regulatory mechanisms using said one or more genetic determinants and protein-protein interaction data.

13. The method of claim 1 , wherein said regulatory mechanism comprises a putative causal gene.

14. The method of claim 1 , further comprising using a false discovery rate procedure to correct for multiple testing.

15. A method for identifying aQTL regions whose genotype modulates transcription factor activity, comprising:

generating, using a computer processor, a promoter affinity profile using a genomic sequence and a position-specific affinity matrix;

generating an inferred transcription factor activity profile using said promoter affinity profile and a gene expression data set; and

identifying an aQTL region for a transcription factor using said inferred transcription factor activity profile and a genotype data set.

16. The method of claim 15 , further comprising identifying a causal gene within said aQTL region using protein-protein interaction data.

17. The method of claim 15 , wherein said aQTL region is identified using genetic analysis.

18. The method of claim 17 , wherein said genetic analysis is selected from a group consisting of genetic linkage analysis and association analysis.

19. The method of claim 18 , wherein said genetic analysis comprises genetic linkage analysis.

20. The method of claim 19 , wherein said aQTL region is identified using composite interval mapping.

21. The method of claim 19 , wherein said aQTL region is identified using a parametric t-test.

22. The method of claim 19 , wherein said aQTL region is identified using a non-parametric Wilcoxon-Mann-Whitney test.