In breeding, single nucleotide polymorphisms (SNPs) in the genome are often used to predict quantitative phenotypes to assist breeding, thereby improving breeding efficiency. The traditional statistical analysis method is limited by many factors including missing data, and its performance sometimes can not meet the requirements. In this paper, we proposed a multi-scale feature convolutional neural network model (MSF-CNN) to predict plant traits. The model extracted SNP features at three different scales through convolution and analyzed the significance of SNP sites through the weight of the SNPs input into the model. The test results showed that MSF-CNN model performed with higher accuracy than the known methods and other deep learning models in phenotype prediction on the datasets with missing genotypic data. This paper also studied the contribution of genotype to traits through saliency map, and discovered several significant SNP loci. These results showed that, compared with other known methods available at present, the deep learning model proposed in this paper can obtain more accurate prediction results of quantitative phenotypes, and can also effectively and efficiently identify SNPs associated with genome-wide association research.
[1] Zhao Y S, Gowda M, Liu W X, et al. Accuracy of genomic selection in European maize elite breeding populations[J]. Theoretical and Applied Genetics, 2012, 124(4): 769-776. DOI: 10.1007/s00122-011-1745-y.
[2] Spindel J, Begum H, Akdemir D, et al. Genomic selection and association mapping in rice (Oryza sativa): effect of trait genetic architecture, training population composition, marker number and statistical model on accuracy of rice genomic selection in elite, tropical rice breeding lines[J]. PLoS Genetics, 2015, 11(2): e1004982. DOI: 10.1371/journal.pgen.1004982.
[3] Xavier A, Jarquin D, Howard R, et al. Genome-wide analysis of grain yield stability and environmental interactions in a multiparental soybean population[J]. G3-Genes Genomes Genetics, 2018, 8(2): 519-529. DOI: 10.1534/g3.117.300300.
[4] Endelman J B. Ridge regression and other kernels for genomic selection with R package rrBLUP[J]. The Plant Genome, 2011, 4(3): 250-255. DOI: 10.3835/plantgenome2011.08.0024.
[5] Wang J X, Joshi T, Valliyodan B, et al. A Bayesian model for detection of high-order interactions among genetic variants in genome-wide association studies[J]. BMC Genomics, 2015, 16: 1011. DOI: 10.1186/s12864-015-2217-6.
[6] Rutkoski J E, Poland J, Jannink J L, et al. Imputation of unordered markers and the impact on genomic selection accuracy[J]. G3 Genes | Genomes | Genetics, 2013, 3(3): 427-439. DOI: 10.1534/g3.112.005363.
[7] Sapoval N, Aghazadeh A, Nute M G, et al. Current progress and open challenges for applying deep learning across the biosciences[J]. Nature Communications, 2022, 13(1): 1-12. DOI: 10.1038/s41467-022-29268-7.
[8] Tong L, Mitchel J, Chatlin K, et al. Deep learning based feature-level integration of multi-omics data for breast cancer patients survival analysis[J]. BMC Medical Informatics and Decision Making, 2020, 20(1): 225. DOI: 10.1186/s12911-020-01225-8.
[9] Uppu S, Krishna A, Gopalan R P. A deep learning approach to detect SNP interactions[J]. Journal of Software, 2016, 11(10): 965-975. DOI: 10.17706/jsw.11.10.965-975.
[10] Liang Z H, Huang J X, Zeng X, et al. DL-ADR: a novel deep learning model for classifying genomic variants into adverse drug reactions[J]. BMC Medical Genomics, 2016, 9(S2): 48. DOI: 10.1186/s12920-016-0207-4.
[11] Lee G, Nho K, Kang B, et al. Predicting Alzheimer’s disease progression using multi-modal deep learning approach[J]. Scientific Reports, 2019, 9(1): 1-12. DOI: 10.1038/s41598-018-37769-z.
[12] Zingaretti L M, Gezan S A, Ferrão L F V, et al.Exploring deep learning for complex trait genomic prediction in polyploid outcrossing species[J]. Frontiers in Plant Science, 2020, 11: 25. DOI: 10.3389/fpls.2020.00025.
[13] Whalen S, Schreiber J, Noble W S, et al. Navigating the pitfalls of applying machine learning in genomics[J]. Nature Reviews Genetics, 2022, 23(3): 169-181. DOI: 10.1038/s41576-021-00434-9.
[14] Xavier A, Beavis W D, Specht J E, et al. SoyNAM: soybean nested association mapping dataset[DB]. R package version, 2015, 1.
[15] Song Q J, Yan L, Quigley C, et al. Genetic characterization of the soybean nested association mapping population[J]. The Plant Genome, 2017, 10(2): 10.3835/plantgenome,2016. 10.0109. DOI: 10.3835/plantgenome2016.10.0109.
[16] Li Y, Willer C J, Ding J, et al. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes[J]. Genetic Epidemiology, 2010, 34(8): 816-834. DOI: 10.1002/gepi.20533.
[17] Huang G, Liu Z, Van Der Maaten L, et al. Densely connected convolutional networks[C]. 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). July 21-26, 2017, Honolulu, HI, USA. IEEE, 2017: 2261-2269. DOI: 10.1109/CVPR.2017.243.
[18] Zhang X Z, Wang Y F, Shi W S. pCAMP: performance comparison of machine learning packages on the edges[EB/OL]. (2019-06-05) [2023-03-24]. https://arxiv.org/abs/1906.01878.
[19] Simonyan K, Zisserman A. Very deep convolutional networks for large-scale image recognition[EB/OL]. (2014-09-04) [2023-03-24]. https://arxiv.org/abs/1409.1556.
[20] Srivastava N, Hinton G, Krizhevsky A, et al. Dropout: a simple way to prevent neural networks from overfitting[J]. The Journal of Machine Learning Research, 2014, 15(1), 1929-1958.
[21] Liu Y, Wang D L, He F, et al. Phenotype prediction and genome-wide association study using deep convolutional neural network of soybean[J]. Frontiers in Genetics, 2019, 10: 1091. DOI: 10.3389/fgene.2019.01091.
[22] Schmutz J, Cannon S B, Schlueter J, et al. Erratum: genome sequence of the palaeopolyploid soybean[J]. Nature, 2010, 465(7294): 120. DOI: 10.1038/nature08957.
[23] Grant D, Nelson R T, Cannon S B, et al. SoyBase, the USDA-ARS soybean genetics and genomics database[J]. Nucleic Acids Research, 2010, 38(Suppl 1): D843-D846. DOI: 10.1093/nar/gkp798.
[24] Joshi T, Patil K, Fitzpatrick M R, et al. Soybean knowledge base (SoyKB): a web resource for soybean translational genomics[J]. BMC Genomics, 2012, 13(Suppl 1): S15. DOI: 10.1186/1471-2164-13-S1-S15.
[25] Bateman A, Coin L, Durbin R, et al. The Pfam protein families database[J]. Nucleic Acids Research, 2004, 32 (Suppl 1): D138-D141. DOI: 10.1093/nar/gkh121.
[26] Xu Z Y, Wang R K, Kong K K, et al. An APETALA2/ethylene responsive factor transcription factor GmCRF4a regulates plant height and auxin biosynthesis in soybean[J]. Frontiers in Plant Science, 2022, 13: 983650. DOI: 10.3389/fpls.2022.983650.