Title
HiTRACE: high-throughput robust analysis for capillary electrophoresis.
Abstract
Motivation: Capillary electrophoresis (CE) of nucleic acids is a workhorse technology underlying high-throughput genome analysis and large-scale chemical mapping for nucleic acid structural inference. Despite the wide availability of CE-based instruments, there remain challenges in leveraging their full power for quantitative analysis of RNA and DNA structure, thermodynamics and kinetics. In particular, the slow rate and poor automation of available analysis tools have bottlenecked a new generation of studies involving hundreds of CE profiles per experiment. Results: We propose a computational method called high-throughput robust analysis for capillary electrophoresis (HiTRACE) to automate the key tasks in large-scale nucleic acid CE analysis, including the profile alignment that has heretofore been a rate-limiting step in the highest throughput experiments. We illustrate the application of HiTRACE on 13 datasets representing 4 different RNAs, 3 chemical modification strategies and up to 480 single mutant variants; the largest datasets each include 87 360 bands. By applying a series of robust dynamic programming algorithms, HiTRACE outperforms prior tools in terms of alignment and fitting quality, as assessed by measures including the correlation between quantified band intensities between replicate datasets. Furthermore, while the smallest of these datasets required 7-10 h of manual intervention using prior approaches, HiTRACE quantitation of even the largest datasets herein was achieved in 3-12 min. The HiTRACE method, therefore, resolves a critical barrier to the efficient and accurate analysis of nucleic acid structure in experiments involving tens of thousands of electrophoretic bands.
Year
DOI
Venue
2011
10.1093/bioinformatics/btr277
BIOINFORMATICS
Keywords
Field
DocType
quantitative analysis,high throughput,nucleic acid,capillary electrophoresis,dynamic programming algorithm,kinetics,thermodynamics,chemical modification,rate limiting,quantitative method,dna structure
Dynamic programming,High-throughput screening,Nucleic acid structure,Computer science,Automation,Bioinformatics,Nucleic acid,Throughput,Replicate,Capillary electrophoresis
Journal
Volume
Issue
ISSN
27
13
1367-4803
Citations 
PageRank 
References 
8
1.40
4
Authors
7
Name
Order
Citations
PageRank
Sungroh Yoon156678.80
Jinkyu Kim2163.07
Justine Hum381.40
Hanjoo Kim4528.01
Seunghyun Park5669.29
Wipapat Kladwang681.40
Rhiju Das7377.66