1. Accelerating Bioinformatics Algorithms with Reconfigurable Computing Presentation to MAPLD Conference September 2004

2. JYardley.183/MAPLD2004 Overview The Problem –BioInformatics Algorithm: Smith Waterman –Current Implementations The Solution –Viva as a Reconfigurable Computing SW & HW Design Tool –Hypercomputer Architecture for High-End RC applications The Implementation –Smith Waterman Viva Code –Smith Waterman Pipeline Design –Smith Waterman Pipeline applied to Hypercomputer Architecture –Smith Waterman Pipeline Primitives inside the FPGA The Results –Visualization of Rat vs. Human Genetic Code –Informal Benchmarks Other Potential Applications –Seismic Data Processing; Weather Modeling; Image Rendering Page 2

3. JYardley.183/MAPLD2004 The Problem: Enormous Biosciences Problems Exploding Datasets in Biosciences: DNA Sequencing Gene Expression Protein Identification Page 3

4. JYardley.183/MAPLD2004 The Need: High-Speed High Sensitivity Algorithms High-Speed High-Sensitivity DNA and Protein Searching Algorithms –Critical in virtually every branch of molecular biology. –Smith-Waterman: Theoretically optimal for sequence matching. BUT Compute Intensive! –BLAST and FASTA: Approximations. Faster than Smith Waterman, but less sensitive. Page 4

5. JYardley.183/MAPLD2004 The Need: High-Speed High Sensitivity Algorithms Comparative Genomics: Comparing the genomes of related species –Identifying genes, defining gene structure, elucidating evolutionary change, identifying regulatory elements and revealing combinatorial control of gene regulation Sequencing Effort –Human sequence is completed; other organisms now being sequenced –Sequencing effort will require high sensitivity DNA searches and alignments –SmithWaterman preferred method of choice—more accurate, specific –NCBI BLAST, WU BLAWST not effective in low-coverage DNA situations RNA interference (RNAi): seeking novel therapies & developing new drugs. –The process: Choosing the correct genetic sequence to effectively block a targeted messenger RNA (mRNA) without silencing additional genes –Due to word length limitations, BLAST algorithms can miss sequences that have one or more mismatches compared to the query siRNA sequence Genome Annotation –BLAST does not allow for long introns or frameshifts –Smith-Waterman is both frameshift- and intron-tolerant. Page5

6. JYardley.183/MAPLD2004 The Need: High-Speed Smith Waterman Large Matrix comparison Large datasets High level of detail for each SW calculation NOT heuristic approximations Page 6

7. JYardley.183/MAPLD2004 The Need: High Performance Biosciences Platform Cluster Computing—most widely used platform. BUT there are diminishing returns: –Expensive to build, difficult to maintain –Require significant power, air conditioning, and physical space –Architecture inherently limits scalability and performance Reconfigurable Computing(RC)—the promising alternative –Advantages of a Custom Chip: Implement algorithms directly in hardware Performance advantages of an ASIC, but without chip development cost –Advantages of a General Purpose Platform Development time comparable to software development FPGAs can be reconfigured to perform other computational tasks. Page 7

8. JYardley.183/MAPLD2004 The Solution FPGA-Programming Environment: Viva VIVA GRAPHICAL LANGUAGE –Capture natively parallel code –Accommodate data of any type, size, or precision –Tune algorithms for speed of execution or conservation of hardware resources VIVA EDITOR –Call Viva algorithms from legacy code such as C, C++, or Fortran –Interactively debug code –Import/Export EDIF files VIVA COMPILER/SYNTHESIZER –Program multi-million gate designs –Compile hardware designs quickly for efficient development VIVA LIBRARIES –Reuse flexible Viva objects which accept any data type or size –Target any hardware platform with a ‘System Description’ – Prototype Viva on any X-86-based Windows machine Page 8

9. JYardley.183/MAPLD2004 The Solution: FPGA-based Hypercomputers Page 9

10. JYardley.183/MAPLD2004 Structure of an FPGA Processing Element Page 10

11. JYardley.183/MAPLD2004 Structure of a Processing Element Quad Page 11

12. JYardley.183/MAPLD2004 Structure of a Hypercomputer Accelerator Board Page 12

13. JYardley.183/MAPLD2004 The Prototype Implementation: Smith Waterman in Viva Code Page 13

14. JYardley.183/MAPLD2004 Smith Waterman Program Flow As the query sequence is loaded, the Init_Cells object creates our initial column and stores it in SW_Cell_Mem. After this initialization period, SW_Cell_Mem will provide a cell to the chain SW_Iteration objects every clock cycle. It will also write a newly calculated cell every clock cycle. The SW_Cell_Mem object stores every n th column, where n is the number of SW_Iteration objects. Page 14

15. JYardley.183/MAPLD2004 Smith Waterman Cells There are as many cells as there are characters in the query sequence. The array of cells represent a column of the scoring matrix. The initial (zero) column is initialized and stored into the cell memory object, SW_Cell_Mem. Each cell contains the following four parameters: –Pattern – a character from the query sequence –Score – the score of this cell in the current i,j position –PatternStart – the position in the query sequence from which the score was calculated –DataStart – the position in the reference sequence from which the score was calculated Page 15

16. JYardley.183/MAPLD2004 Cell Data Types Data Element size may be adjusted depending on usage: –Pattern – contains as many bits as needed to encode characters from the sequences – 4 bits for nucleotides. –Score and PatternStart – Equal in size. Must be large enough to encode the number of entries in the query sequence –DataStart – will be the largest data set as it must be able to encode any position in the reference sequence. Right size for the job: –Less circuitry is needed to calculate matches in smaller sequences. –Smaller sequences may exploit more parallelism. Page 16

17. JYardley.183/MAPLD2004 In this example, our Pattern contains 4 bits, for modeling nucleotides. The Score and PatternStart parameters contain 26 bits, so our query sequence may contain up to 67,108,864 characters. The DataStart parameter contains 27 bits, meaning our reference sequence may contain up to 134,217,728 characters. Smith Waterman Data Sets Page 17

18. JYardley.183/MAPLD2004 Smith Waterman Iteration Page 18

19. JYardley.183/MAPLD2004 SW_Iteration Object Inputs: –Matrix_In: receives a constant stream of cells. It is imperative for efficiency that the pipe remains full. –Data: receives a single character from the reference sequence. The cells computed will be for the column of the scoring matrix corresponding to the Data value. –CountBy: the radix of the algorithm (number of iteration objects) –Init_J_In: this iteration object’s index in the chain of iteration objects –ClkG: System Clock –Token_In: a token pulse precedes a set of cells, allowing the iteration object to clear-out data from the previous set of cells –Init: initialization pulse utilized only before search commences –G: accompanies each valid cell Page 19

20. JYardley.183/MAPLD2004 SW_Iteration Object Outputs: –Matrix_Out: newly-computed cell –Token_Out: passes token to next iteration object –D: accompanies each newly-computed cell –Init_J_Out: used by next iteration object –I & J: current row and column – used to report results Page 20

21. JYardley.183/MAPLD2004 Pipe Stages The SW_Iteration object contains four pipe stages. A cell is received by and produced by the SW_Iteration object every clock cycle. When a cell enters, it is coming from the previous column, so its values are those of the West neighbor. Since the cell in the row above any given cell is in the next pipe stage, access to both the North and Northwest neighbors’ values are possible. Page 21

22. JYardley.183/MAPLD2004 Parallelism If a given hardware system has enough physical resources to accommodate n SW_Iteration objects, the Smith Waterman program may operate on n columns in parallel. Hence n cells are computed every clock cycle. Each Virtex II 6000 can support 64 iteration objects Page 22

23. JYardley.183/MAPLD2004 The Implementation: Pipeline Primitives Inside the FPGA Page 23

24. JYardley.183/MAPLD2004 PE2 XPE Data Distribution XPR Router Bus Controller X86 System PE1 (Controller) PE3PE4PE5PE6PE7PE8 The Implementation: Smith Waterman Pipeline Page 24

25. JYardley.183/MAPLD2004 The Results: Rat vs. Human Genetic Code Page 25

26. JYardley.183/MAPLD2004 The Results: Bacteria to Bacteria Comparison Page 26

27. JYardley.183/MAPLD2004 The Results: Informal Statistics Total # Operations / Second –1 Smith-Waterman Step includes: 25 Logic Operations (Adds, compares, mostly 26-27 bit ops, some single bit ops) 13 Data Reorder Operations (Move, Combine…) 11 Data Stor (Assignment) –Logic Operations Only: 25 Ops * 25Mhz * 448 Smith-Waterman kernels = 280Billion Operations / Second –Logic & Data Operations: 49 Ops * 25Mhz * 448 Smith-Waterman kernels = 550Billion Operations / Second Total Aggregate Communications Bandwidth of Systolic Array –12 * 88 * 25Mhz = 26.4 Gb/s plus 7 * 22 * 50Mhz = 7Gb/s = 34.1 Gb/s Resources Consumed / Resources Available –PE2 – PE7: 60% to 70% consumed –PE1 20% consumed; XPE 5%; XPR.1% Compilation time –# Gates: 70 Million Total –Time to compile: 20 Minutes Power Consumption –Meter—50 Watts Page 27

28. JYardley.183/MAPLD2004 Summary & Conclusions This Viva prototype of the Smith-Waterman algorithm demonstrates that the algorithm can be parallelized for fast operation in an FPGA system and validates the usage of FPGAs to increase the speed of the Smith-Waterman algorithm compared to clusters Speed of the Prototype: –An HC-62 has the bandwidth to pass cells between 7 FPGAs, allowing for 448 parallel SW_Iteration objects –At a conservative 30 Mhz system clock speed, this gives 30,000 * 448 = 13.4 Billion Smith Waterman steps/second. Opportunities to further optimize the algorithm include: –Increasing the number of SW_Iterations that can be done in parallel (up to 100 Billion Smith Waterman steps/second) –Increasing the clock speed of the hardware (up to 1 Trillion Smith Waterman steps/second) Page 28