  Motivation: Eugene Myers in his string graph paper (Myers, 2005) suggested
that in a string graph or equivalently a unitig graph, any path spells a valid
assembly. As a string/unitig graph also encodes every valid assembly of reads,
such a graph, provided that it can be constructed correctly, is in fact a
lossless representation of reads. In principle, every analysis based on
whole-genome shotgun sequencing (WGS) data, such as SNP and insertion/deletion
(INDEL) calling, can also be achieved with unitigs.
  Results: To explore the feasibility of using de novo assembly in the context
of resequencing, we developed a de novo assembler, fermi, that assembles
Illumina short reads into unitigs while preserving most of information of the
input reads. SNPs and INDELs can be called by mapping the unitigs against a
reference genome. By applying the method on 35-fold human resequencing data, we
showed that in comparison to the standard pipeline, our approach yields similar
accuracy for SNP calling and better results for INDEL calling. It has higher
sensitivity than other de novo assembly based methods for variant calling. Our
work suggests that variant calling with de novo assembly be a beneficial
complement to the standard variant calling pipeline for whole-genome
resequencing. In the methodological aspects, we proposed FMD-index for
forward-backward extension of DNA sequences, a fast algorithm for finding all
super-maximal exact matches and one-pass construction of unitigs from an
FMD-index.
  Availability: http://github.com/lh3/fermi
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