Winnowing DNA for Rare Sequences: Highly Specific Sequence and Methylation Based Enrichment

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue

ABC(SMC) 2: simultaneous inference and model checking of chemical reaction networks

We present an approach that simultaneously infers model parameters while statistically verifying properties of interest to chemical reaction networks, which we observe through data and we model as parametrised continuous-time Markov Chains. The new approach simultaneously integrates learning models from data, done by likelihood-free Bayesian inference, specifically Approximate Bayesian Computation, with formal verification over models, done by statistically model checking properties expressed as logical specifications (in CSL). The approach generates a probability (or credibility calculation) on whether a given chemical reaction network satisfies a property of interest