Alignment-free comparison of next-generation sequencing data using   compression-based distance measures
  Enormous volumes of short reads data from next-generation sequencing (NGS) technologies have posed new challenges to the area of genomic sequence comparison.   The multiple sequence alignment approach is hardly applicable to NGS data due to the challenging problem of short read assembly.   Thus alignment-free methods need to be developed for the comparison of NGS samples of short reads.   Recently, new $k$-mer based distance measures such as {\it CVTree}, $d_{2}^{S}$, {\it co-phylog} have been proposed to address this problem.   However, those distances depend considerably on the parameter $k$, and how to choose the optimal $k$ is not trivial since it may depend on different aspects of the sequence data.   Hence, in this paper we consider an alternative parameter-free approach: compression-based distance measures.   These measures have shown impressive performance on long genome sequences in previous studies, but they have not been tested on NGS short reads.   In this study we perform extensive validation and show that the compression-based distances are highly consistent with those distances obtained from the $k$-mer based methods, from the alignment-based approach, and from existing benchmarks in the literature.   Moreover, as these measures are parameter-free, no optimization is required and they still perform consistently well on multiple types of sequence data, for different kinds of species and taxonomy levels.   The compression-based distance measures are assembly-free, alignment-free, parameter-free, and thus represent useful tools for the comparison of long genome sequences and NGS samples of short reads. 
Ngoc Hieu Tran, Xin Chen
q-bio.GN