LTC: A novel algorithm to improve the efficiency of contig assembly for physical mapping in complex genomes

Zeev Frenkel, Etienne Paux, David Mester, Catherine Feuillet, Abraham Korol

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Physical maps are the substrate of genome sequencing and map-based cloning and their construction relies on the accurate assembly of BAC clones into large contigs that are then anchored to genetic maps with molecular markers. High Information Content Fingerprinting has become the method of choice for large and repetitive genomes such as those of maize, barley, and wheat. However, the high level of repeated DNA present in these genomes requires the application of very stringent criteria to ensure a reliable assembly with the FingerPrinted Contig (FPC) software, which often results in short contig lengths (of 3-5 clones before merging) as well as an unreliable assembly in some difficult regions. Difficulties can originate from a non-linear topological structure of clone overlaps, low power of clone ordering algorithms, and the absence of tools to identify sources of gaps in Minimal Tiling Paths (MTPs).Results: To address these problems, we propose a novel approach that: (i) reduces the rate of false connections and Q-clones by using a new cutoff calculation method; (ii) obtains reliable clusters robust to the exclusion of single clone or clone overlap; (iii) explores the topological contig structure by considering contigs as networks of clones connected by significant overlaps; (iv) performs iterative clone clustering combined with ordering and order verification using re-sampling methods; and (v) uses global optimization methods for clone ordering and Band Map construction. The elements of this new analytical framework called Linear Topological Contig (LTC) were applied on datasets used previously for the construction of the physical map of wheat chromosome 3B with FPC. The performance of LTC vs. FPC was compared also on the simulated BAC libraries based on the known genome sequences for chromosome 1 of rice and chromosome 1 of maize.Conclusions: The results show that compared to other methods, LTC enables the construction of highly reliable and longer contigs (5-12 clones before merging), the detection of "weak" connections in contigs and their "repair", and the elongation of contigs obtained by other assembly methods.

Original languageEnglish
Article number584
JournalBMC Bioinformatics
Volume11
DOIs
StatePublished - 30 Nov 2010

Bibliographical note

Funding Information:
The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under the grant agreement FP7-212019 (TriticeaeGenome project, http:// www.triticeaegenome.eu). It was also partially supported by Binational Agricultural Research and Development Fund (BARD research project US-3873-06) and by the Israeli Ministry of Absorption.

ASJC Scopus subject areas

  • Applied Mathematics
  • Molecular Biology
  • Structural Biology
  • Biochemistry
  • Computer Science Applications

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