Title
GRASS: a generic algorithm for scaffolding next-generation sequencing assemblies.
Abstract
Motivation: The increasing availability of second-generation high-throughput sequencing (HTS) technologies has sparked a growing interest in de novo genome sequencing. This in turn has fueled the need for reliable means of obtaining high-quality draft genomes from short-read sequencing data. The millions of reads usually involved in HTS experiments are first assembled into longer fragments called contigs, which are then scaffolded, i.e. ordered and oriented using additional information, to produce even longer sequences called scaffolds. Most existing scaffolders of HTS genome assemblies are not suited for using information other than paired reads to perform scaffolding. They use this limited information to construct scaffolds, often preferring scaffold length over accuracy, when faced with the tradeoff. Results: We present GRASS (GeneRic ASsembly Scaffolder)-a novel algorithm for scaffolding second-generation sequencing assemblies capable of using diverse information sources. GRASS offers a mixed-integer programming formulation of the contig scaffolding problem, which combines contig order, distance and orientation in a single optimization objective. The resulting optimization problem is solved using an expectation-maximization procedure and an unconstrained binary quadratic programming approximation of the original problem. We compared GRASS with existing HTS scaffolders using Illumina paired reads of three bacterial genomes. Our algorithm constructs a comparable number of scaffolds, but makes fewer errors. This result is further improved when additional data, in the form of related genome sequences, are used.
Year
DOI
Venue
2012
10.1093/bioinformatics/bts175
BIOINFORMATICS
Keywords
Field
DocType
quadratic program,next generation sequencing,expectation maximization,bacterial genome,generic algorithm,optimization problem,genome sequence
Genome,Hybrid genome assembly,Scaffold,Computer science,Contig,DNA sequencing,Artificial intelligence,Bioinformatics,Optimization problem,Machine learning,Bacterial genome size,Genetic algorithm
Journal
Volume
Issue
ISSN
28
11
1367-4803
Citations 
PageRank 
References 
13
0.67
17
Authors
4
Name
Order
Citations
PageRank
Alexey A. Gritsenko1163.13
Jurgen F. Nijkamp2383.03
Marcel J. T. Reinders31556104.09
Dick de Ridder478872.24