Nanopore Event-Transduction Signal Stabilization for Wide pH Range under Extreme Chaotrope Conditions.

Operation of an α-hemolysin nanopore transduction detector is found to be surprisingly robust over a critical range of pH (6-9), including physiological pH = 7.4 and polymerase chain reaction (PCR) pH = 8.4, and extreme chaotrope concentration, including 5 M urea.

The NTD Nanoscope: potential applications and implementations.

Background: Nanopore transduction detection (NTD) offers prospects for a number of highly sensitive and discriminative applications, including: (i) single nucleotide polymorphism (SNP) detection; (ii) targeted DNA re-sequencing; (iii) protein isoform assaying; and (iv) biosensing via antibody or aptamer coupled molecules. Nanopore event transduction involves single-molecule biophysics, engineered information flows, and nanopore cheminformatics. The NTD Nanoscope has seen limited use in the scientific community, however, due to lack of information about potential applications, and lack of availability for the device itself.

Pattern recognition-informed feedback for nanopore detector cheminformatics.

Pattern recognition-informed (PRI) feedback using channel current cheminformatics (CCC) software is shown to be possible in "real-time" experimental efforts. The accuracy of the PRI classification is shown to inherit the high accuracy of our offline classifier: 99.9% accuracy in distinguishing between terminal base pairs of two DNA hairpins.

Clustering ionic flow blockade toggles with a mixture of HMMs.

Background: Ionic current blockade signal processing, for use in nanopore detection, offers a promising new way to analyze single molecule properties with potential implications for DNA sequencing. The alpha-Hemolysin transmembrane channel interacts with a translocating molecule in a nontrivial way, frequently evidenced by a complex ionic flow blockade pattern with readily distinguishable modes of toggling. Effective processing of such signals requires developing machine learning methods capable of learning the various blockade modes for classification and knowledge discovery purposes.