Exact parallel alignment of megabase genomic sequences with tunable work distribution

Sequence Alignment is a basic operation in Bioinformatics that is performed thousands of times, on daily basis. The exact methods for pairwise alignment have quadratic time complexity. For this reason, heuristic methods such as BLAST are widely used. To obtain exact results faster, parallel strategies have been proposed but most of them fail to align huge biological sequences. This happens because not only the quadratic time must be considered but also the space should be reduced. In this paper, we evaluate the performance of Z-align, a parallel exact strategy that runs in user-restricted memory space. Also, we propose and evaluate a tunable work distribution mechanism. The results obtained in two clusters show that two sequences of size 24MBP (Mega Base Pairs) and 23MBP, respectively, were successfully aligned with Z-align. Also, in order to align two 3MBP sequences, a speedup of 34.35 was achieved for 64 processors. The evaluation of our work distribution mechanism shows that the execution times can be sensibly reduced when appropriate parameters are chosen. Finally, when comparing Z-align with BLAST, it is clear that, in many cases, Z-align is able to produce alignments with higher score

High Performance Biological Pairwise Sequence Alignment: FPGA versus GPU versus Cell BE versus GPP

This paper explores the pros and cons of reconfigurable computing in the form of FPGAs for high performance efficient computing. In particular, the paper presents the results of a comparative study between three different acceleration technologies, namely, Field Programmable Gate Arrays (FPGAs), Graphics Processor Units (GPUs), and IBM’s Cell Broadband Engine (Cell BE), in the design and implementation of the widely-used Smith-Waterman pairwise sequence alignment algorithm, with general purpose processors as a base reference implementation. Comparison criteria include speed, energy consumption, and purchase and development costs. The study shows that FPGAs largely outperform all other implementation platforms on performance per watt criterion and perform better than all other platforms on performance per dollar criterion, although by a much smaller margin. Cell BE and GPU come second and third, respectively, on both performance per watt and performance per dollar criteria. In general, in order to outperform other technologies on performance per dollar criterion (using currently available hardware and development tools), FPGAs need to achieve at least two orders of magnitude speed-up compared to general-purpose processors and one order of magnitude speed-up compared to domain-specific technologies such as GPUs

Space Efficient Sequence Alignment for SRAM-Based Computing: X-Drop on the Graphcore IPU

Dedicated accelerator hardware has become essential for processing AI-based workloads, leading to the rise of novel accelerator architectures. Furthermore, fundamental differences in memory architecture and parallelism have made these accelerators targets for scientific computing. The sequence alignment problem is fundamental in bioinformatics; we have implemented the $X$-Drop algorithm, a heuristic method for pairwise alignment that reduces search space, on the Graphcore Intelligence Processor Unit (IPU) accelerator. The $X$-Drop algorithm has an irregular computational pattern, which makes it difficult to accelerate due to load balancing. Here, we introduce a graph-based partitioning and queue-based batch system to improve load balancing. Our implementation achieves $10\times$ speedup over a state-of-the-art GPU implementation and up to $4.65\times$ compared to CPU. In addition, we introduce a memory-restricted $X$-Drop algorithm that reduces memory footprint by $55\times$ and efficiently uses the IPU's limited low-latency SRAM. This optimization further improves the strong scaling performance by $3.6\times$.Comment: 12 pages, 7 figures, 2 table

Extreme Scale De Novo Metagenome Assembly

Metagenome assembly is the process of transforming a set of short, overlapping, and potentially erroneous DNA segments from environmental samples into the accurate representation of the underlying microbiomes's genomes. State-of-the-art tools require big shared memory machines and cannot handle contemporary metagenome datasets that exceed Terabytes in size. In this paper, we introduce the MetaHipMer pipeline, a high-quality and high-performance metagenome assembler that employs an iterative de Bruijn graph approach. MetaHipMer leverages a specialized scaffolding algorithm that produces long scaffolds and accommodates the idiosyncrasies of metagenomes. MetaHipMer is end-to-end parallelized using the Unified Parallel C language and therefore can run seamlessly on shared and distributed-memory systems. Experimental results show that MetaHipMer matches or outperforms the state-of-the-art tools in terms of accuracy. Moreover, MetaHipMer scales efficiently to large concurrencies and is able to assemble previously intractable grand challenge metagenomes. We demonstrate the unprecedented capability of MetaHipMer by computing the first full assembly of the Twitchell Wetlands dataset, consisting of 7.5 billion reads - size 2.6 TBytes.Comment: Accepted to SC1

Ultra-large alignments using Phylogeny-aware Profiles

Many biological questions, including the estimation of deep evolutionary histories and the detection of remote homology between protein sequences, rely upon multiple sequence alignments (MSAs) and phylogenetic trees of large datasets. However, accurate large-scale multiple sequence alignment is very difficult, especially when the dataset contains fragmentary sequences. We present UPP, an MSA method that uses a new machine learning technique - the Ensemble of Hidden Markov Models - that we propose here. UPP produces highly accurate alignments for both nucleotide and amino acid sequences, even on ultra-large datasets or datasets containing fragmentary sequences. UPP is available at https://github.com/smirarab/sepp.Comment: Online supplemental materials and data are available at http://www.cs.utexas.edu/users/phylo/software/upp

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

MC64-ClustalWP2: A Highly-Parallel Hybrid Strategy to Align Multiple Sequences in Many-Core Architectures

We have developed the MC64-ClustalWP2 as a new implementation of the Clustal W algorithm, integrating a novel parallelization strategy and significantly increasing the performance when aligning long sequences in architectures with many cores. It must be stressed that in such a process, the detailed analysis of both the software and hardware features and peculiarities is of paramount importance to reveal key points to exploit and optimize the full potential of parallelism in many-core CPU systems. The new parallelization approach has focused into the most time-consuming stages of this algorithm. In particular, the so-called progressive alignment has drastically improved the performance, due to a fine-grained approach where the forward and backward loops were unrolled and parallelized. Another key approach has been the implementation of the new algorithm in a hybrid-computing system, integrating both an Intel Xeon multi-core CPU and a Tilera Tile64 many-core card. A comparison with other Clustal W implementations reveals the high-performance of the new algorithm and strategy in many-core CPU architectures, in a scenario where the sequences to align are relatively long (more than 10 kb) and, hence, a many-core GPU hardware cannot be used. Thus, the MC64-ClustalWP2 runs multiple alignments more than 18x than the original Clustal W algorithm, and more than 7x than the best x86 parallel implementation to date, being publicly available through a web service. Besides, these developments have been deployed in cost-effective personal computers and should be useful for life-science researchers, including the identification of identities and differences for mutation/polymorphism analyses, biodiversity and evolutionary studies and for the development of molecular markers for paternity testing, germplasm management and protection, to assist breeding, illegal traffic control, fraud prevention and for the protection of the intellectual property (identification/traceability), including the protected designation of origin, among other applications