TCGA data

DNA sequencing

• Cost of sequencing has gone down a lot, faster than Moore’s law.
• Next generation sequencing is really cheap.
• Lots of data

Sequencing protocol

• fragment the DNA (sound?)
• library preparation
• amplify (PCR)
• sequence (cDNA library -> bridge amplification)
• fluorescent dye binds to terminal nucleotide on cDNA
• fastq is the output (reads + qualities)

Mutations

How do you reliably “call” genotype variants given a large error rate (~1%-0.1%)

“calling” a variant refers to assigning a nucleotide as a mutation or non-mutation.

Bayes law

$$ P(H|D) = \frac{P(H)P(D|H)}{\sum_h P(H) P(D|H)} $$

probabilistic model that is optimized iteratively based on observations. Assumes independence.