Dataset Information

A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings.

ABSTRACT: Optical mapping by direct visualization of individual DNA molecules, stretched in nanochannels with sequence-specific fluorescent labeling, represents a promising tool for disease diagnostics and genomics. An important challenge for this technique is thermal motion of the DNA as it undergoes imaging; this blurs fluorescent patterns along the DNA and results in information loss. Correcting for this effect (a process referred to as kymograph alignment) is a common preprocessing step in nanochannel-based optical mapping workflows, and we present here a highly efficient algorithm to accomplish this via pattern recognition. We compare our method with the one previous approach, and we find that our method is orders of magnitude faster while producing data of similar quality. We demonstrate proof of principle of our approach on experimental data consisting of melt mapped bacteriophage DNA.

SUBMITTER: Noble C

PROVIDER: S-EPMC4395267 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings.

Noble Charleston C Nilsson Adam N AN Freitag Camilla C Beech Jason P JP Tegenfeldt Jonas O JO Ambjörnsson Tobias T

PloS one 20150413 4

Optical mapping by direct visualization of individual DNA molecules, stretched in nanochannels with sequence-specific fluorescent labeling, represents a promising tool for disease diagnostics and genomics. An important challenge for this technique is thermal motion of the DNA as it undergoes imaging; this blurs fluorescent patterns along the DNA and results in information loss. Correcting for this effect (a process referred to as kymograph alignment) is a common preprocessing step in nanochannel ...[more]

PMID: 25875920

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Project description:Computational pan-genomics utilizes information from multiple individual genomes in large-scale comparative analysis. Genetic variation between case-controls, ethnic groups, or species can be discovered thoroughly using pan-genomes of such subpopulations. Whole-genome sequencing (WGS) data volumes are growing rapidly, making genomic data compression and indexing methods very important. Despite current space-efficient repetitive sequence compression and indexing methods, the deployed compression methods are often sequential, computationally time-consuming, and do not provide efficient sequence alignment performance on vast collections of genomes such as pan-genomes. For performing rapid analytics with the ever-growing genomics data, data compression and indexing methods have to exploit distributed and parallel computing more efficiently. Instead of strict genome data compression methods, we will focus on the efficient construction of a compressed index for pan-genomes. Compressed hybrid-index enables fast sequence alignments to several genomes at once while shrinking the index size significantly compared to traditional indexes. We propose a scalable distributed compressed hybrid-indexing method for large genomic data sets enabling pan-genome-based sequence search and read alignment capabilities. We show the scalability of our tool, DHPGIndex, by executing experiments in a distributed Apache Spark-based computing cluster comprising 448 cores distributed over 26 nodes. The experiments have been performed both with human and bacterial genomes. DHPGIndex built a BLAST index for n = 250 human pan-genome with an 870:1 compression ratio (CR) in 342 minutes and a Bowtie2 index with 157:1 CR in 397 minutes. For n = 1,000 human pan-genome, the BLAST index was built in 1520 minutes with 532:1 CR and the Bowtie2 index in 1938 minutes with 76:1 CR. Bowtie2 aligned 14.6 GB of paired-end reads to the compressed (n = 1,000) index in 31.7 minutes on a single node. Compressing n = 13,375,031 (488 GB) GenBank database to BLAST index resulted in CR of 62:1 in 575 minutes. BLASTing 189,864 Crispr-Cas9 gRNA target sequences (23 MB in total) to the compressed index of human pan-genome (n = 1,000) finished in 45 minutes on a single node. 30 MB mixed bacterial sequences were (n = 599) were blasted to the compressed index of 488 GB GenBank database (n = 13,375,031) in 26 minutes on 25 nodes. 78 MB mixed sequences (n = 4,167) were blasted to the compressed index of 18 GB E. coli sequence database (n = 745,409) in 5.4 minutes on a single node.

Dataset Information

A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings.

Publications

A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings.

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