Accurate determination of node and arc multiplicities in de bruijn graphs using conditional random fields.

ABSTRACT

BACKGROUND: De Bruijn graphs are key data structures for the analysis of next-generation sequencing data. They efficiently represent the overlap between reads and hence, also the underlying genome sequence. However, sequencing errors and repeated subsequences render the identification of the true underlying sequence difficult. A key step in this process is the inference of the multiplicities of nodes and arcs in the graph. These multiplicities correspond to the number of times each k-mer (resp. k+1-mer) implied by a node (resp. arc) is present in the genomic sequence. Determining multiplicities thus reveals the repeat structure and presence of sequencing errors. Multiplicities of nodes/arcs in the de Bruijn graph are reflected in their coverage, however, coverage variability and coverage biases render their determination ambiguous. Current methods to determine node/arc multiplicities base their decisions solely on the information in nodes and arcs individually, under-utilising the information present in the sequencing data. RESULTS: To improve the accuracy with which node and arc multiplicities in a de Bruijn graph are inferred, we developed a conditional random field (CRF) model to efficiently combine the coverage information within each node/arc individually with the information of surrounding nodes and arcs. Multiplicities are thus collectively assigned in a more consistent manner. CONCLUSIONS: We demonstrate that the CRF model yields significant improvements in accuracy and a more robust expectation-maximisation parameter estimation. True k-mers can be distinguished from erroneous k-mers with a higher F1 score than existing methods. A C++11 implementation is available at https//github.com/biointec/detox under the GNU AGPL v3.0 license.