Indexing large genome collections on a PC

Motivation: The availability of thousands of invidual genomes of one species should boost rapid progress in personalized medicine or understanding of the interaction between genotype and phenotype, to name a few applications. A key operation useful in such analyses is aligning sequencing reads against a collection of genomes, which is costly with the use of existing algorithms due to their large memory requirements. Results: We present MuGI, Multiple Genome Index, which reports all occurrences of a given pattern, in exact and approximate matching model, against a collection of thousand(s) genomes. Its unique feature is the small index size fitting in a standard computer with 16--32\,GB, or even 8\,GB, of RAM, for the 1000GP collection of 1092 diploid human genomes. The solution is also fast. For example, the exact matching queries are handled in average time of 39\,$\mu$s and with up to 3 mismatches in 373\,$\mu$s on the test PC with the index size of 13.4\,GB. For a smaller index, occupying 7.4\,GB in memory, the respective times grow to 76\,$\mu$s and 917\,$\mu$s. Availability: Software and Suuplementary material: \url{http://sun.aei.polsl.pl/mugi}

Reference Based Genome Compression

DNA sequencing technology has advanced to a point where storage is becoming the central bottleneck in the acquisition and mining of more data. Large amounts of data are vital for genomics research, and generic compression tools, while viable, cannot offer the same savings as approaches tuned to inherent biological properties. We propose an algorithm to compress a target genome given a known reference genome. The proposed algorithm first generates a mapping from the reference to the target genome, and then compresses this mapping with an entropy coder. As an illustration of the performance: applying our algorithm to James Watson's genome with hg18 as a reference, we are able to reduce the 2991 megabyte (MB) genome down to 6.99 MB, while Gzip compresses it to 834.8 MB.Comment: 5 pages; Submitted to the IEEE Information Theory Workshop (ITW) 201

RLZAP: Relative Lempel-Ziv with Adaptive Pointers

Relative Lempel-Ziv (RLZ) is a popular algorithm for compressing databases of genomes from individuals of the same species when fast random access is desired. With Kuruppu et al.'s (SPIRE 2010) original implementation, a reference genome is selected and then the other genomes are greedily parsed into phrases exactly matching substrings of the reference. Deorowicz and Grabowski (Bioinformatics, 2011) pointed out that letting each phrase end with a mismatch character usually gives better compression because many of the differences between individuals' genomes are single-nucleotide substitutions. Ferrada et al. (SPIRE 2014) then pointed out that also using relative pointers and run-length compressing them usually gives even better compression. In this paper we generalize Ferrada et al.'s idea to handle well also short insertions, deletions and multi-character substitutions. We show experimentally that our generalization achieves better compression than Ferrada et al.'s implementation with comparable random-access times

The similarity metric

A new class of distances appropriate for measuring similarity relations between sequences, say one type of similarity per distance, is studied. We propose a new ``normalized information distance'', based on the noncomputable notion of Kolmogorov complexity, and show that it is in this class and it minorizes every computable distance in the class (that is, it is universal in that it discovers all computable similarities). We demonstrate that it is a metric and call it the {\em similarity metric}. This theory forms the foundation for a new practical tool. To evidence generality and robustness we give two distinctive applications in widely divergent areas using standard compression programs like gzip and GenCompress. First, we compare whole mitochondrial genomes and infer their evolutionary history. This results in a first completely automatic computed whole mitochondrial phylogeny tree. Secondly, we fully automatically compute the language tree of 52 different languages.Comment: 13 pages, LaTex, 5 figures, Part of this work appeared in Proc. 14th ACM-SIAM Symp. Discrete Algorithms, 2003. This is the final, corrected, version to appear in IEEE Trans Inform. T

Dynamic Relative Compression, Dynamic Partial Sums, and Substring Concatenation

Given a static reference string $R$ and a source string $S$, a relative compression of $S$ with respect to $R$ is an encoding of $S$ as a sequence of references to substrings of $R$. Relative compression schemes are a classic model of compression and have recently proved very successful for compressing highly-repetitive massive data sets such as genomes and web-data. We initiate the study of relative compression in a dynamic setting where the compressed source string $S$ is subject to edit operations. The goal is to maintain the compressed representation compactly, while supporting edits and allowing efficient random access to the (uncompressed) source string. We present new data structures that achieve optimal time for updates and queries while using space linear in the size of the optimal relative compression, for nearly all combinations of parameters. We also present solutions for restricted and extended sets of updates. To achieve these results, we revisit the dynamic partial sums problem and the substring concatenation problem. We present new optimal or near optimal bounds for these problems. Plugging in our new results we also immediately obtain new bounds for the string indexing for patterns with wildcards problem and the dynamic text and static pattern matching problem