Title
DNA Sequencing via Quantum Mechanics and Machine Learning
Abstract
Rapid sequencing of individual human genome is prerequisite to genomic medicine, where diseases will be prevented by preemptive cures. Quantum-mechanical tunneling through single-stranded DNA in a solid-state nanopore has been proposed for rapid DNA sequencing, but unfortunately the tunneling current alone cannot distinguish the four nucleotides due to large fluctuations in molecular conformation and solvent. Here, we propose a machine-learning approach applied to the tunneling current-voltage (I-V) characteristic for efficient discrimination between the four nucleotides. We first combine principal component analysis (PCA) and fuzzy c-means (FCM) clustering to learn the "fingerprints" of the electronic density-of-states (DOS) of the four nucleotides, which can be derived from the I-V data. We then apply the hidden Markov model and the Viterbi algorithm to sequence a time series of DOS data (i.e., to solve the sequencing problem). Numerical experiments show that the PCA-FCM approach can classify unlabeled DOS data with 91% accuracy. Furthermore, the classification is found to be robust against moderate levels of noise, i.e., 70% accuracy is retained with a signal-to-noise ratio of 26 dB. The PCA-FCM-Viterbi approach provides a 4-fold increase in accuracy for the sequencing problem compared with PCA alone. In conjunction with recent developments in nanotechnology, this machine-learning method may pave the way to the much-awaited rapid, low-cost genome sequencer.
Year
Venue
Keywords
2010
Clinical Orthopaedics and Related Research
quantitative method,principal component analysis,genome sequence,viterbi algorithm,quantum mechanics,dna sequence,electron density,signal to noise ratio,nucleotides,hidden markov model,human genome,time series,machine learning
Field
DocType
Volume
Genome,Computer science,Fuzzy logic,Artificial intelligence,DNA sequencing,Human genome,Cluster analysis,Hidden Markov model,Machine learning,Principal component analysis,Viterbi algorithm
Journal
abs/1012.0
ISSN
Citations 
PageRank 
International Journal of Computational Science, Vol. 4, No. 4, 2010. pp. 352 - 370
0
0.34
References 
Authors
3
7
Name
Order
Citations
PageRank
Henry Yuen1339.52
Fuyuki Shimojo29513.89
Kevin J. Zhang313.52
Ken-ichi Nomura413213.36
Rajiv K. Kalia523935.66
Aiichiro Nakano627947.53
Priya Vashishta724337.69