1. From Kolmogorov and Shannon to Bioinformatics and Grid Computing Raffaele Giancarlo Dipartimento di Matematica, Università di Palermo

2. Aim Give a flavour of fundamental novel discoveries about indexing and compression: A string, and any compact encoding of it, is the best index for itself Give a flavour of some fundamental novel discoveries about Distance functions and Classification, particularly relevant for Bioinformatics On the way, mention uses of :suffix trees, suffix arrays, Burrows- Wheelet Transform, Move to Front… In 30 min. an incredibly long jurney: From Kolmogorov and Shannon to Grid Computing References: available on-line

3. What do we mean by “Indexing” ? Raw sequence of characters or bytes Types of data Types of query Character-based query Indexing approaches : Full-text indexes, » Suffix Array, Suffix tree,… DNA sequences Audio-video files Executables Arbitrary substring

4. What do we mean by “Compression” ? Any Algorithm that squezes data : lossless, lossy  From March 2001 the Memory eXpansion Technology (MXT) is available on IBM eServers x330MXT Same performance of a PC with double memory but at half cost Moral: More economical to store data in compressed form than uncompressed » CPU speed nowadays makes (de)compression “costless” !!

5. What we mean by “Classification” ? Any tool that can group “related” objects together, e.g. the unaligned mithocondrial genomes NCBI Classfication

6. Compression and Indexing : Two sides of the same coin !  Do we witness a paradoxical situation ? An index injects redundant data, in order to speed up the pattern searches Compression removes redundancy, in order to squeeze the space occupancy NO, new results proved a mutual reinforcement behaviour ! Better indexes can be designed by exploiting compression techniques Better compressors can be designed by exploiting indexing techniques In terms of space occupancyAlso in terms of compression ratio Classification is the “third side” of the coin: Kolmogorov Complexity, Information Theory, Compression and Indexing

7. Our journey, today... Suffix Array (1990) Index design (Weiner ’73)Compressor design (Shannon ’48) Burrows-Wheeler Transform (1994) Compressed Index -Space close to gzip, bzip - Query time close to O(|P|) Compression Booster Tool to transform a poor compressor into a better compression algorithm Universal Distances and Classification Kolmogorov

8. Investigate Indexing ideas  Compressor design First Lap…in record time!!! Booster

9. Key Idea 1: Suffix Tree [Weiner 73, McCreight 76, Ukkonen 92] String: mississippi# 12 1 # i pm s 119 # ppi# ssi 52 ppi# ssippi# 109 i# pi# i si 74 ppi# ssippi# 63 ppi# ssippi#

10. pi#mississi p ppi#mississ i sippi#missi s sissippi#mi s ssippi#miss i ssissippi#m i issippi#mis s mississippi # ississippi# m Key Idea 2: Burrows-Wheeler Compression (1994) Let us be given a string s = mississippi# mississippi# ississippi#m ssissippi#mi sissippi#mis sippi#missis ippi#mississ ppi#mississi pi#mississip i#mississipp #mississippi ssippi#missi issippi#miss Sort the rows #mississipp i i#mississip p ippi#missis s bwt(s) s

11. Burrows and Wheeler Compression Why it works: BWT creates a locally homogeneous string: abaababa bbbaaaaa MTF transforms it into a globally homegeneous sequence of integers bbbaaaaa 00010000 The final string is “easy” to compress Experimentally: compressibility is proportional to % of zeros

12. Qualitatively, it can be shown: c’ is shorter than c, if s is compressible Time( A boost ) = Time ( A ), i.e. no slowdown A is used as a black-box Boosting [Ferragina, Giancarlo, Manzini, Sciortino, 03,04,05] The technique takes a poor compressor A and turns it into a compressor A boost with better performance guarantee c’c’ Booster The better is A, the better is A boost A sc The more compressible is s, the better is A boost

13. We investigated: Index Ideas  Compression design Let’s now turn to the other direction Compression ideas  Index design Second Lap…Even faster Compressed Indexes

14. Rotated text #mississipp i#mississip ippi#missis issippi#mis ississippi# mississippi pi#mississi ppi#mississ sippi#missi sissippi#mi ssippi#miss ssissippi#m #mississipp i#mississip ippi#missis issippi#mis ississippi# mississippi pi#mississi ppi#mississ sippi#missi sissippi#mi ssippi#miss ssissippi#m Suffix Array vs. BW-transform ipssm#pissiiipssm#pissii L 12 11 8 5 2 1 10 9 7 4 6 3 SA L includes SA and T. Can we search within L ? mississippi

15. A compressed index [Ferragina-Manzini, IEEE Focs 2000] In practice, the index is much appealing: Space close to the best known compressors, ie. bzip Query time of few millisecs on hundreds of MBs The theoretical result: Query complexity: O(p + occ log  N) time Space occupancy: O( N H k (T) ) + o(N) bits k-th order empirical entropy

16. Universal Distances and Classification Third Lap…

17. Large Data Sets Classification of Sequences on a Genome-wide Scale Distances based on alignments are either not applicable or too slow Fast and reliable alignment-free methods are badly needed Classification of Proteins, both for Function and Structure- Lagging behind to sequence data

18. Proteins and Their String Representations Amino acid sequence (FASTA format); Atomic coordinates (Atom lines)‏;

19. Protein Representations Topologic Models (Top Diagrams)‏

20. Kolmogorov Complexity The Kolmogorov Complexity K(x) of a string x is defined as the length of the shortest binary program that produces x. The conditional Kolmogorov Complexity K(x|y) represents the minimum amount of information required to generate x by an effective computation when y is given as an input to the computation. The Kolmogorov Complexity K(x,y) of a pair objects x and y is the length of the shortest binary program that produces x and y and a way to tell them apart.

21. Universal Similarity metric (USM)‏ Problem: USM(x,y) is based on Kolmogorov Complexity that is non- computable in the Turing sense. Solution: K(x) can be approximated via data compression by using its relationship with Shannon Information Theory. USM is a methodology rather than a formula quantifying the similarity of two strings.

22. Approximations of USM K(x) can be approximated by C(x), K(x,y) by C(xy) and K(x|y*) by C(xy) – C(x). We obtain three approximations to USM: where

23. Experiments [Ferragina, Giancarlo, Greco, Manzini, Valiente, 2007 ] Experimental setup: Five Benchmarck datasets of proteins (several alternative representations); A benchmark dataset of Genomic sequences (complete unaligned mitochondrial Genomes)‏; Twenty-five compression algorithms; Three dissimilarity functions based on USM. Two set of experiments to compare USM both with methods based on alignments and not: via ROC Analysis; via UPGMA and NJ.

24. An example Unaligned mitochondrial DNA complete Genomes

25. Results and Conclusions Useful Guidelines for Use of USM Methodilogy for Biological Investigation Which compressor to use Which among UCD,NCD and CD to use Which data representation is best Etc…

26. Software Kolmogorov Library: http://www.math.unipa.it/~raffaele/kolmogorov/ Sequential processing is too slow even for relatively small data sets, i.e, 278 files (1.5Mb) classification takes 12 hours on a state of the art PC…half an hour on Grid Soon Available as a Grid-aware Web Service on COMETA Portal

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