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Allele & SNP Scans Module

scan.Rmd

Developer’s Guide to the qtl2shiny Package

Overview

The Allele & SNP Scans panel helps researchers run genome scans to identify QTL signals and overlay high-density variant mappings to narrow down candidate genes. It integrates:

  1. scanDataApp: Generates founder-allele-based genome scans (LOD and BLUP curves).
  2. snpGeneApp: Performs high-density SNP association scans, annotations, and gene/exon coordinate views.

Module Hierarchy & Entrypoints

  • Top-Level Container:
    • Standalone Application: scanApp()
    • Server Module: scanServer(id, hotspot_list, snp_list, probs_obj, project_df)
    • UI Input: scanInput(id)
    • UI Output: scanOutput(id)
  • Allele Scan Sub-Modules:
    • Allele Scan Data (scanDataApp): Computes and plots allele LOD/BLUP scans. Server: scanDataServer.
  • SNP & Gene Sub-Modules:
    • SNP/Gene Subpanel (snpGeneApp): Server: snpGeneServer.
    • SNP Plot (snpPlotApp): Renders Manhattan SNP plots. Server: snpPlotServer.
    • SNP Table (snpTableApp): Searchable variants datatable. Server: snpTableServer.
    • Gene region (geneRegionApp): Displays gene tracks. Server: geneRegionServer.
    • Exon detail (geneExonApp): Exon structure database lookup. Server: geneExonServer.

1. Top-Level Container (scanApp)

Server Logic & Reactive Flow (scanServer)

The panel coordinates coordinates from the hotspot_list$win_par global sidebar, queries allele coefficients, and handles download outputs:

  1. Instantiation:
    • Calls scanDataServer to handle founder allele calculations.
    • Calls snpGeneServer to coordinate high-density associations and gene annotation overlays.
  2. Download Handling:
    • Routes plot/table downloads by checking input$hap_tab:
      • scan: Downloads plots/tables of allele-based genome scans.
      • snp: Downloads SNP plots, tables, gene maps, or exon charts.
graph TD
    HotspotList[hotspot_list] --> scanServer
    SnpList[snp_list] --> scanServer
    Probs[probs_obj] --> scanServer
    
    scanServer --> scanData[scanDataServer]
    scanServer --> snpGene[snpGeneServer]
    
    snpGene --> snpPlot[snpPlotServer]
    snpGene --> snpTable[snpTableServer]
    snpGene --> geneRegion[geneRegionServer]
    snpGene --> geneExon[geneExonServer]

2. Allele Genome Scans (scanDataApp)

Data Used

  • Genotype Probabilities (probs_obj): disk-backed multi-point probabilities loaded via probsServer.
  • LOCO Kinship Matrices: kinship objects corresponding to the active chromosome (hotspot_list$kinship_list).
  • Phenotypes & Covariates: hotspot_list$pheno_mx and hotspot_list$covar_df.

Logic and Code Workflow

  1. QTL Scanning:
    • Computes QTL genome scans using qtl2::scan1() for the selected phenotype, accounting for covariates and kinship models.
  2. Founder BLUPs/Coefficients:
    • Runs linear regression mapping founder coefficients along chromosomes to show direction and magnitude of effects.
  3. Plotting:
    • Renders LOD or BLUP curves.

3. SNP Association & Gene Mapping (snpGeneApp & Sub-modules)

Data Used

  • SNP Probabilities SQLite DB (cc-variants.sqlite): High-density variants query function (query_variants).
  • Gene Annotation SQLite DB (mouse_genes_mgi.sqlite): Database listing gene boundaries (query_genes).

Logic and Code Workflow

  1. SNP Scan & Association:
    • Collaborates with snpListServer which collapses founder probabilities into SNP patterns (snpprob_collapse).
    • Runs fast association mappings (scan1covar) to calculate SNP LOD scores.
  2. Manhattan Plots (snpPlotServer):
    • Plots SNP LOD scores vs. coordinates in Mbp.
  3. Gene Overlay (geneRegionServer):
    • Queries query_genes and maps structural genes inside the chromosomal window.
  4. Exon Structure (geneExonApp):
    • Evaluates user clicks on candidate genes to pull transcript profiles, mapping coding/non-coding exons.