Abstract
The discovery of higher-order epistatic interactions is an important task in the field of genome wide association studies which allows for the identification of complex interaction patterns between multiple genetic markers. Some existing bruteforce approaches explore the whole space of k-interactions in an exhaustive manner resulting in almost intractable execution times. Computational cost can be reduced drastically by restricting the search space with suitable preprocessing filters which prune unpromising candidates. Other approaches mitigate the execution time by employing massively parallel accelerators in order to benefit from the vast computational resources of these architectures. In this paper, we combine a novel preprocessing filter, namely SingleMI, with massively parallel computation on modern GPUs to further accelerate epistasis discovery. Our implementation improves both the runtime and accuracy when compared to a previous GPU counterpart that employs mutual information clustering for prefiltering. SingleMI is open source software and publicly available at: https://github.com/sleeepyjack/singlemi/.
Similar content being viewed by others
References
Buckles, B.P., Lybanon, M.: Algorithm 515: generation of a vector from the lexicographical index [G6]. ACM Trans. Math. Softw. 3(2), 180–182 (1977)
Cattaert, T., Calle, M.L., Dudek, S.M., Hohn, J.M., Lishout, F.V., Urrea, V., Ritchie, M.D., Steel, K.V.: Model-based multifactor dimensionality reduction for detecting epistasis in case-control data in the presence of noise. Ann. Hum. Genet. 75(1), 78–89 (2011)
Cordell, H.J.: Epistasis: what it means, what it doesn’t mean, and statistical methods to detect it in humans. Hum. Mol. Genet. 11(20), 2463–2468 (2002)
Cordell, H.J.: Detecting gene-gene interactions that underlie human diseases. Nat. Rev. Genet. 10(6), 392–404 (2009)
Culverhouse, R.: The use of the restricted partition method with case-control data. Hum. Hered. 63(2), 93–100 (2007)
Duane Merrill, N.C.: CUB documentation. https://nvlabs.github.io/cub/ (2016)
Easton, D.F., Pooley, K.A., et al.: Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148), 1087–1093 (2007)
Frayling, T.M., Timpson, N.J., et al.: A common variant in the fto gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826), 889–894 (2007)
González-Domínguez, J., Schmidt, B.: GPU-accelerated exhaustive search for third-order epistatic interactions in case-control studies. J. Comput. Sci. 8, 93–100 (2015)
González-Domínguez, J., Ramos, S., Touriño, J., Schmidt, B.: Parallel pairwise epistasis detection on heterogeneous computing architectures. IEEE Trans. Parallel Distrib. Syst. 27(8), 2329–2340 (2016)
Goudey, B., Abedini, M., Hopper, J.L., Inouye, M., Makalic, E., Schmidt, D.F., Wagner, J., Zhou, Z., Zobel, J., Reumann, M.: High performance computing enabling exhaustive analysis of higher order single nucleotide polymorphism interaction in genome wide association studies. Health Inf. Sci. Syst. 3(Suppl 1), S3 (2015)
Gui, J., Andrew, A.S., Andrews, P., et al.: A robust multifactor dimensionality reduction method for detecting gene-gene interactions with application to the genetic analysis of bladder cancer susceptibility. Ann. Hum. Genet. 75(1), 20–28 (2011)
Guo, X., Meng, Y., Yu, N., Pan, Y.: Cloud computing for detecting high-order genome-wide epistatic interaction via dynamic clustering. BMC Bioinform. 15(1), 102 (2014)
Hu, X., Liu, Q., Zhang, Z., Li, Z., Wang, S., He, L., Shi, Y.: SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm, efficiently reveals the risk genetic epistasis in bipolar disorder. Cell Res. 20(7), 854–857 (2010)
Jünger, D.: CUDA batch reduce primitive. https://github.com/sleeepyjack/batchreduce (2016)
Jünger, D., Hundt, C., González-Domínguez, J., Schmidt, B.: Ultra-fast detection of higher-order epistatic interactions on gpus. In: 4th International Workshop on Parallelism in Bioinformatics (PBio 2016), Grenoble, France (2016)
Kam-Thong, T., Czamara, D., Tsuda, K., Borgwardt, K., Lewis, C., Erhardt-Lehmann, A., Hemmer, B., Rieckmann, P., Daake, M., Weber, F., Wolf, C., Ziegler, A., Pütz, B., Holsboer, F., Schölkopf, B., Müller-Myhsok, B.: EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units. Eur. J. Hum. Genet. 19(4), 465–471 (2011)
Kässens, J.C., Wienbrandt, L., González-Domínguez, J., Schmidt, B., Schimmler, M.: High-speed exhaustive 3-locus interaction epistasis analysis on FPGAs. J. Comput. Sci. 9, 131–136 (2015)
Leem, S., Jeong, H.H., et al.: Fast detection of high-order epistatic interactions in genome-wide association studies using information theoretic measure. Comput. Biol. Chem. 50, 19–28 (2014)
Lloyd, S.: Least squares quantization in PCM. IEEE Trans. Inf. Theory 28(2), 129–137 (1982)
Meng, Y.A., Yu, Y., Cupples, L.A., Farrer, L.A., Lunetta, K.L.: Performance of random forest when SNPs are in linkage disequilibrium. BMC Bioinform. 10(1), 1 (2009)
Nelson, M.R., Kardia, S.L., Ferrel, L.E., Sing, C.F.: A combinatorial partitioning method to identify multilocus genotypic partitions that predict quantitative trait variation. Genome Res. 11(3), 458–470 (2001)
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., Sham, P.C.: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81(3), 559–575 (2007)
Ritchie Lab: genomeSIMLA software. https://ritchielab.psu.edu/software/genomesimla-download (2016)
Sluga, D., Curk, T., Zupan, B., Lotric, U.: Heterogeneous computing architecture for fast detection of SNP-SNP interactions. BMC Bioinform. 15(1), 216 (2014)
Tuo, S., Zhang, J., Yuan, X., Zhang, Y., Liu, Z.: FHSA-SED: two-locus model detection for genome-wide association study with harmony search algorithm. PLoS ONE 11(3), 1–27 (2016)
Wan, X., Yang, C., et al.: BOOST: a fast approach to detecting gene-gene interactions in genome-wide case-control studies. Am. J. Hum. Genet. 87(3), 325–340 (2010)
Wan, X., Yang, C., et al.: Predictive rule inference for epistatic interaction detection in genome-wide association studies. Bioinformatics 26(1), 30–37 (2010)
Wang, Y., Liu, G., Feng, M., Wong, L.: An empirical comparison of several recent epistatic interaction detection methods. Bioinformatics 27(21), 2936–2943 (2011)
Xie, M., Li, J., Jiang, T.: Detecting genome-wide epistases based on the clustering of relatively frequent items. Bioinformatics 28(1), 5–12 (2012)
Yang, Y., Houle, A.M., Letendre, J., Richter, A.: RET Gly691ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from Quebec. Hum. Mutat. 29(5), 695–702 (2008)
Yang, C., He, Z., Wan, X., Yang, Q., Xue, H., Weichuan, Y.: SNPHarvester: a filtering-based approach for detecting epistatic interactions in genome-wide association studies. Bioinformatics 25(4), 504–511 (2009)
Yung, L.S., Yang, C., Wan, X., Yu, W.: GBOOST: a GPU-based tool for detecting genegene interactions in genomewide case control studies. Bioinformatics 27(9), 1309–1310 (2011)
Zhang, Y., Liu, J.S.: Bayesian inference of epistatic interactions in case-control studies. Nat. Genet. 39(9), 1167–1173 (2007)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jünger, D., Hundt, C., Domínguez, J.G. et al. Speed and accuracy improvement of higher-order epistasis detection on CUDA-enabled GPUs. Cluster Comput 20, 1899–1908 (2017). https://doi.org/10.1007/s10586-017-0938-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10586-017-0938-9