RESUMO
Picoamperage signals are generated as each nucleotide of a DNA or RNA molecule is ratcheted through a nanosequencer's nanopores by motor proteins. These are segmented into step-current level signals, "squiggles", representing the nucleotide sequence. It has been suggested that applying dynamic time warp Barycentre Averaging (DBA) to multiple noisy squiggles can generate a lower noise, less-distorted, consensus signal that retains the key squiggle characteristics that would be distorted by other averaging approaches. We discuss experimental results obtained when developing DBA consensus signals from squiggles produced by an Oxford MinION nanosequencer squiggle convertor during an Enolase study. Metrics are proposed to identify differences between the known gold standard and consensus signals, and the level of self-consistency between consensus signals developed from noisy squiggles with different length distortions. A number of location-specific differences between the gold and consensus squiggles were identified.
Assuntos
Nanoporos , ConsensoRESUMO
Epigenetics is a chemical modification to DNA without changes in the base sequence. While it is known that epigenetic modifications have far reaching implications on how genes are expressed, it is difficult to identify what the modification is or where it can be found. A next-generation method of sequencing called nanopore sequencing may be the solution. Nanopore sequencing runs a voltage bias across the DNA sequence and outputs a unique electric response to each genetic unit. Epigenetic modifications may then be identified by their distinct electric response. In this paper we provide preliminary results of applying dynamic time warp Barycenter Averaging (DBA) to multiple noisy nanopore streams to generate a consensus signal that can be used to identify genetic sequences and their modifications. DBA convergence rates, time complexity, together with qualitative and quantitative metrics to compare the consensus signal with gold standards are evaluated.