Calculating rapid genome changes
Prof. Judith Berman
Dept. Molecular Microbiology & Biotechnology
Data Sciences Meeting
December 24, 2015
Rapid responses to drugs
• Cells become drug resistant MUCH faster than we
expect based on rare mutations subject to
selection pressure
• What are the mechanisms?
– Aneuploidy (unbalanced numbers of chromosomes)
– Loss of heterozygosity (LOH, homozygosis of alleles)
• How can we detect this and visualize it in an
intuitive manner?
Measuring aneuploidy by DNA copy number
Detecting heterozygosity
(2 different sequences at same locus)
• SNP data:
• Heterozygous (a/b)
a/b
Probe
count
a/b
Microarray : SNP ratios
• Whole genome ploidy.
• Chr copy numbers.
• SNP ratios.
• SNP data:
• Heterozygous (a/b)
• Homozygous (a/a or b/b)
a/a
Probe
count
a/a
b/b
b/b
Microarray : SNP ratios
• Whole genome ploidy.
• Chr copy numbers.
• SNP ratios.
• SNP data:
• Heterozygous (a/b)
• Homozygous (a/a or b/b)
• Trisomic (a/a/b or a/b/b)
a/a/b
Probe
count
a/a/b
a/b/b
a/b/b
Data Integration
•
•
•
•
Whole genome ploidy.
Chr copy numbers.
SNP ratios.
SNP data.
• Data integration:
• CNVs
Data Integration
•
•
•
•
Whole genome ploidy.
Chr copy numbers.
SNP ratios.
SNP data.
• Data integration:
• CNVs
• Heterozygous
• a/b
Data Integration
•
•
•
•
Whole genome ploidy.
Chr copy numbers.
SNP ratios.
SNP data.
• Data integration:
• CNVs
• Heterozygous
• a/b
• Homozygous
• a/a
• b/b
Data Integration
•
•
•
•
Whole genome ploidy.
Chr copy numbers.
SNP ratios.
SNP data.
• Data integration:
• CNVs
• Heterozygous
• a/b
• Homozygous
• a/a
• b/b
• Trisomic
• a/a/b
• a/b/b
Unrelated Clinical Isolates
• Loss of heterozygosity (LOH), manually highlighted in yellow.
• Reference strain SC5314.
Unrelated Clinical Isolates
• Loss of heterozygosity (LOH), manually highlighted in yellow.
• Reference strain SC5314.
• Selection of clinical isolates, diverse LOHs.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Related Clinical Isolates
• Loss of heterozygosity (LOH), automatically highlighted in yellow.
• Change in allelic ratios, highlighted in blue.
Future plans
• Use YMAP to display other types of data
– RNA seq
– RAD seq
• Adapt YMAP to analyze additional organisms
• Link YMAP analysis to other programs (e.g., IGV)
• Develop new applications for visualizing
genome structure and composition