BXD-STR-Mutator-Manuscript

Notebooks for generating figures and results are in the analysis/ directory.

Part 1: Identifying new mutations in the BXD family

1. analysis/stats.sh

Computes some general statistics:

• Total number of TRs: 1,176,016
• Total number of STRs: 1,154,738
• Total number of VNTRs: 21,278

Part 2: Mapping quantitative trait loci for STR mutation phenotypes

2. analysis/1_denovo_strs.Rmd

Computes statistics:

• Number of unique loci with mutations: 18,119
• Number of STRs: 18,053
• Number of VNTRs: 66
• Excess of mutations on B haplotypes: 52.5%
• Percent of mutated loci that are singletons: 57.6%

Figures:

• 1b: distribution of sizes of mutations
• 1c: Proportion new mutations by epoch
• Supp Figure 1: karyoplot with locations of new mutations
• Supp Figure 2: properties of mutations by repeat unit length
• Supp Figure 3: number of strains with new mutations per locus

3. analysis/2_mutator_pheno_scan.Rmd

Computes statistics:

• Total number of LD-pruned SNPs: 7,101
• Max LOD (all): 6.1
• LOD center and interval (all): 79.7, 91.2, 93.4
• Max LOD (tetra): 8.4
• LOD center and interval (tetra): 89.4, 90.4, 93.4
• Z-test proportions by epoch

Figures:

• 2b: Expansion propensity vs. B/D
• 2c: Expansion propensity vs. B/D by epoch
• Supp Figure 4: Genic vs intergenic regions
• Supp Figure 6: QTL scan by multiple features
• Supp Figure 7: Distribution of exp propensity by period
• Supp Figure 8: QTL scan by epoch

4. analysis/2_mutator_pheno_plots.ipynb

Figures:

• 2a: QTL signal
• 2d: zoom in on trace for QTL signal
• Supp Figure 5: zoom in on trace for modest peaks

5. analysis/2_prep_suppdata.ipynb

• prepares Supplementary Datasets 1-3
• Generates auto_info used by 2_mutation_patterns

6. analysis/2_mutation_patterns.ipynb

Figures:

• 2e: mutation rate vs. length
• 2f: expansion propensity vs. length
• Supp Figure 9: mutation patterns
• Supp Figure 10: motif analysis

Computes statistics:

• Z-test proportions by repeat unit length
• Correlation of repeat length vs. mutation rate
• Correlation of repeat length vs. expansion propensity

7. analysis/2_sex_chroms.ipynb

Figures:

• Supp Figure 11: sex chroms

Computes statistics:

• Total number of sex chromosome mutations and loci
• Z test for sex chroms

Part 3: Analysis of candidate variants disrupting protein-coding genes

8. analysis/3_vep_annot_per_gene.Rmd

Figures:

• 3a: variants in Msh3
• 3b: zoom in on 5' end
• Supp Figure 13: Variant selection
• Supp Figure 14: Variant selection zoom in on Msh3
• Supp Table 1: VEP summary
• Supp Table 2: VEP impactful variants (DNA repair genes)
• Supp Table 4: LOD scores and VEP for SVs

Computes statistics:

• Number of STRs/SNPs/SVs in QTL interval overlapping protein coding genes

Large files required for 3_vep_annot_per_gene.Rmd can be downloaded here: https://drive.google.com/drive/folders/1cVm7IZPHZ3gl4O4yi_GQ_Jz5pz3gChpi?usp=sharing

Part 4: Expansion propensity QTL co-localizes with multiple cis-eQTLs

9. analysis/4_eqtl_mapping.Rmd

Figures:

• Supp Figure 16: Redo QTL with subsets
• Supp Figure 17: summary of availability of expression datasets
• Supp Figure 19: summary of eQTL results
• Supp Figure 20a: detailed eQTL traces for DNA repair genes
• Supp Figure 21: co-localization of QTL/eQTL signals
• 4a: traces of best eQTL signals

10. analysis/4_gene_expr.Rmd

Figures:

• Supp Figure 15: summary of expression levels
• Supp Figure 20b: detailed per-dataset expression levels for DNA repair
• 4b: expression diffs for dna repair genes

11. analysis/4_eqtl_by_probe.Rmd

Figures:

• Supp Figure 18: probe-level analysis for Msh3
• Supp Figure 22: Detailed probe-level analysis of Msh3