Embedded CMOS basecalling for nanopore DNA sequencing

DNA sequencing based on nanopore sensors is now entering the marketplace. The ability to interface this technology to established CMOS microelectronics promises significant improvements in functionality and miniaturization. Among the key functions to benefit from this interface will be basecalling, the conversion of raw electronic molecular signatures to nucleotide sequence predictions. This paper presents the design and performance potential of custom CMOS base-callers embedded alongside nanopore sensors. A basecalliing architecture implemented in 32-nm technology is discussed with the ability to process the equivalent of 20 human genomes per day in real-time at a power density of 5 W/cm2 assuming a 3-mer nanopore sensor.

[1]  Hugo Y. K. Lam,et al.  Detecting and annotating genetic variations using the HugeSeq pipeline , 2012, Nature Biotechnology.

[2]  C. Arun,et al.  A Low Power and High Speed Viterbi Decoder Based on Deep Pipelined, Clock Blocking and Hazards Filtering , 2009, Int. J. Commun. Netw. Syst. Sci..

[3]  Martin Kircher,et al.  Improved base calling for the Illumina Genome Analyzer using machine learning strategies , 2009, Genome Biology.

[4]  Lloyd M. Smith,et al.  Fluorescence detection in automated DNA sequence analysis , 1986, Nature.

[5]  Paul C. Boutros,et al.  Nanocall: An Open Source Basecaller for Oxford Nanopore Sequencing Data , 2016 .

[6]  John F. Mulley,et al.  Assessing the utility of the Oxford Nanopore MinION for snake venom gland cDNA sequencing , 2015, PeerJ.

[7]  P. Glenn Gulak,et al.  A multiprocessor architecture for Viterbi decoders with linear speedup , 1993, IEEE Trans. Signal Process..

[8]  Andrew J. Viterbi,et al.  Error bounds for convolutional codes and an asymptotically optimum decoding algorithm , 1967, IEEE Trans. Inf. Theory.

[9]  Aleksei Aksimentiev,et al.  DNA base-calling from a nanopore using a Viterbi algorithm. , 2012, Biophysical journal.

[10]  Rajendra D. Pendse,et al.  Implementation of Pad Circuitry for Radially Staggered Bond Pad Arrangements , 1996 .

[11]  D. Branton,et al.  Characterization of individual polynucleotide molecules using a membrane channel. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Barry Merriman,et al.  Progress in Ion Torrent semiconductor chip based sequencing , 2012, Electrophoresis.

[13]  Klaus Schulten,et al.  Detection and Quantification of Methylation in DNA using Solid-State Nanopores , 2013, Scientific Reports.

[14]  G R Willmott,et al.  Comment on 'Modeling the conductance and DNA blockade of solid-state nanopores'. , 2012, Nanotechnology.

[15]  Erika Check Hayden,et al.  The automated lab , 2014, Nature.

[16]  A. Mikheyev,et al.  A first look at the Oxford Nanopore MinION sequencer , 2014, Molecular ecology resources.

[17]  Gernot Heiser,et al.  An Analysis of Power Consumption in a Smartphone , 2010, USENIX Annual Technical Conference.

[18]  R. R. Spencer,et al.  Comparison of different detection techniques for digital magnetic recording channels , 1995 .

[19]  William J. Dally,et al.  Digital systems engineering , 1998 .

[20]  Yaniv Erlich A vision for ubiquitous sequencing , 2015, bioRxiv.

[21]  David A. Matthews,et al.  Real-time, portable genome sequencing for Ebola surveillance , 2016, Nature.

[22]  Rashid Bashir,et al.  Nanopore-based assay for detection of methylation in double-stranded DNA fragments. , 2015, ACS nano.

[23]  Tomáš Vinař,et al.  DeepNano: Deep recurrent neural networks for base calling in MinION nanopore reads , 2016, PloS one.

[24]  Tim Massingham,et al.  All Your Base: a fast and accurate probabilistic approach to base calling , 2012, Genome Biology.

[25]  P. Glenn Gulak,et al.  A VLSI implementation of a cascade Viterbi decoder with traceback , 1993, 1993 IEEE International Symposium on Circuits and Systems.

[26]  Yun S. Song,et al.  BayesCall: A model-based base-calling algorithm for high-throughput short-read sequencing. , 2009, Genome research.

[27]  Michael L. Klein,et al.  Discrimination of methylcytosine from hydroxymethylcytosine in DNA molecules. , 2011, Journal of the American Chemical Society.

[28]  Haris Vikalo,et al.  OnlineCall: fast online parameter estimation and base calling for illumina's next-generation sequencing , 2012, Bioinform..

[29]  R. Bashir,et al.  Nanopore sensors for nucleic acid analysis. , 2011, Nature nanotechnology.

[30]  Trieu-Kien Truong,et al.  A VLSI design for a trace-back Viterbi decoder , 1992, IEEE Trans. Commun..

[31]  Ghavam G. Shahidi Evolution of CMOS Technology at 32 nm and Beyond , 2007, 2007 IEEE Custom Integrated Circuits Conference.

[32]  K. Lieberman,et al.  Processive replication of single DNA molecules in a nanopore catalyzed by phi29 DNA polymerase. , 2010, Journal of the American Chemical Society.

[33]  S. Turner,et al.  Real-time DNA sequencing from single polymerase molecules. , 2010, Methods in enzymology.

[34]  Peixuan Guo,et al.  Solid-State and Biological Nanopore for Real-Time Sensing of Single Chemical and Sequencing of DNA. , 2013, Nano today.

[35]  Stuart Dreyfus,et al.  Richard Bellman on the Birth of Dynamic Programming , 2002, Oper. Res..

[36]  Cees Dekker,et al.  Modeling the conductance and DNA blockade of solid-state nanopores , 2011, Nanotechnology.

[37]  Ebrahim Ghafar-Zadeh,et al.  High-speed event detector for embedded nanopore bio-systems , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[38]  K. Shepard,et al.  Integrated nanopore sensing platform with sub-microsecond temporal resolution , 2012, Nature Methods.

[39]  Paul Chow,et al.  Generalized cascade Viterbi decoder-a locally connected multiprocessor with linear speed-up , 1991, [Proceedings] ICASSP 91: 1991 International Conference on Acoustics, Speech, and Signal Processing.

[40]  J. Aldrich R.A. Fisher and the making of maximum likelihood 1912-1922 , 1997 .

[41]  Alexander Y. Grosberg,et al.  Reply to Comment on ‘Modeling the conductance and DNA blockade of solid-state nanopores’ , 2012 .