论文信息 - CASAnova: A multiclass support vector machine model for the classification of human sperm motility patterns†

CASAnova: A multiclass support vector machine model for the classification of human sperm motility patterns†

Abstract The ability to accurately monitor alterations in sperm motility is paramount to understanding multiple genetic and biochemical perturbations impacting normal fertilization. Computer-aided sperm analysis (CASA) of human sperm typically reports motile percentage and kinematic parameters at the population level, and uses kinematic gating methods to identify subpopulations such as progressive or hyperactivated sperm. The goal of this study was to develop an automated method that classifies all patterns of human spermmotility during in vitro capacitation following the removal of seminal plasma. We visually classified CASA tracks of 2817 sperm from 18 individuals and used a support vector machine-based decision tree to compute four hyperplanes that separate five classes based on their kinematic parameters. We then developed a web-based program, CASAnova, which applies these equations sequentially to assign a single classification to each motile sperm. Vigorous sperm are classified as progressive, intermediate, or hyperactivated, and nonvigorous sperm as slow or weakly motile. This program correctly classifies sperm motility into one of five classes with an overall accuracy of 89.9%. Application of CASAnova to capacitating sperm populations showed a shift from predominantly linear patterns of motility at initial time points to more vigorous patterns, including hyperactivated motility, as capacitation proceeds. Both intermediate and hyperactivated motility patterns were largely eliminated when sperm were incubated in noncapacitating medium, demonstrating the sensitivity of this method. The five CASAnova classifications are distinctive and reflect kinetic parameters of washed human sperm, providing an accurate, quantitative, and high-throughput method for monitoring alterations in motility. Summary Sentence A CASA-based support vector machine model of human sperm motility provides rapid, accurate, and quantitative analysis of all motile sperm in a population.

[1] Summer G. Goodson,et al. Sperm function, protein phosphorylation, and metabolism differ in mice lacking successive sperm-specific glycolytic enzymes† , 2017, Biology of reproduction.

[2] David L. Aylor,et al. Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross , 2017, Genetics.

[3] A. Salicioni,et al. Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models , 2016, Scientific Reports.

[4] D. A. O’Brien,et al. Structural analyses to identify selective inhibitors of glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme. , 2016, Molecular human reproduction.

[5] M. Yeste,et al. Effect of Pseudomonas aeruginosa on sperm capacitation and protein phosphorylation of boar spermatozoa. , 2016, Theriogenology.

[6] K. Borgwardt,et al. Machine Learning in Medicine , 2015, Mach. Learn. under Resour. Constraints Vol. 3.

[7] Chia-Yu Kao,et al. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction , 2015, G3: Genes, Genomes, Genetics.

[8] Melissa R. Miller,et al. Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa , 2015, Human reproduction.

[9] B. Lee,et al. Comparative Cytotoxicity and Sperm Motility Using a Computer-Aided Sperm Analysis System (CASA) for Isomers of Phthalic Acid, a Common Final Metabolite of Phthalates , 2015, Journal of toxicology and environmental health. Part A.

[10] A. Salicioni,et al. Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways , 2015, Journal of cellular physiology.

[11] Michael I. Jordan,et al. Machine learning: Trends, perspectives, and prospects , 2015, Science.

[12] E. Baldi,et al. Quantification of CatSper1 expression in human spermatozoa and relation to functional parameters. , 2015, Human reproduction.

[13] David Mortimer,et al. The future of computer-aided sperm analysis , 2015, Asian journal of andrology.

[14] Songying Zhang,et al. Heat Shock Protein 90 Has Roles in Intracellular Calcium Homeostasis, Protein Tyrosine Phosphorylation Regulation, and Progesterone-Responsive Sperm Function in Human Sperm , 2014, PloS one.

[15] O. Mehrpour,et al. Occupational exposure to pesticides and consequences on male semen and fertility: a review. , 2014, Toxicology letters.

[16] P. Wyatt,et al. Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity , 2014, Human reproduction.

[17] Ahmet Gudeloglu,et al. Medical Management of Male Infertility in the Absence of a Specific Etiology , 2014, Seminars in Reproductive Medicine.

[18] A. Salicioni,et al. Impaired Sperm Maturation in Rnase9 Knockout Mice1 , 2014, Biology of reproduction.

[19] E. Baldi,et al. The CatSper calcium channel in human sperm: relation with motility and involvement in progesterone-induced acrosome reaction. , 2014, Human reproduction.

[20] J. Starmer,et al. Mitochondrial Hydrogen Peroxide and Defective Cholesterol Efflux Prevent In Vitro Fertilization by Cryopreserved Inbred Mouse Sperm1 , 2013, Biology of reproduction.

[21] V. Kay,et al. The clinical significance of calcium-signalling pathways mediating human sperm hyperactivation , 2013, Human reproduction.

[22] Summer G. Goodson,et al. Metabolic Substrates Exhibit Differential Effects on Functional Parameters of Mouse Sperm Capacitation1 , 2012, Biology of reproduction.

[23] D. Mortimer,et al. ESHRE special interest group for andrology basic semen analysis course: a continued focus on accuracy, quality, efficiency and clinical relevance. , 2011, Human reproduction.

[24] Wei Wang,et al. Classification of Mouse Sperm Motility Patterns Using an Automated Multiclass Support Vector Machines Model1 , 2011, Biology of reproduction.

[25] Dejian Ren,et al. Calcium signaling through CatSper channels in mammalian fertilization. , 2010, Physiology.

[26] Wan-Xiang Xu,et al. CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans. , 2010, Human reproduction.

[27] Guy Lapalme,et al. A systematic analysis of performance measures for classification tasks , 2009, Inf. Process. Manag..

[28] S. Suarez,et al. CatSper-null mutant spermatozoa are unable to ascend beyond the oviductal reservoir. , 2009, Reproduction, fertility, and development.

[29] Susan S Suarez,et al. Control of hyperactivation in sperm. , 2008, Human reproduction update.

[30] D. Clapham,et al. All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility , 2007, Proceedings of the National Academy of Sciences.

[31] William Stafford Noble,et al. Support vector machine , 2013 .

[32] Shannon Byers,et al. Performance of ten inbred mouse strains following assisted reproductive technologies (ARTs). , 2006, Theriogenology.

[33] C. Gnoth,et al. Definition and prevalence of subfertility and infertility. , 2005, Human reproduction.

[34] C. Roberts,et al. Consistent presence of two normally distributed sperm subpopulations within normozoospermic human semen: a kinematic study. , 2004, International journal of andrology.

[35] Zheng Rong Yang,et al. Biological applications of support vector machines , 2004, Briefings Bioinform..

[36] M. Ensslin,et al. Mammalian fertilization , 2004, Current Biology.

[37] Y. Sakata,et al. Impaired hyperactivation of human sperm in patients with infertility. , 2004, Journal of medical and dental sciences.

[38] F. Dondero,et al. A new objective method for scoring human sperm hyperactivation based on head axis angle deviation. , 2001, International journal of andrology.

[39] S T Mortimer,et al. CASA--practical aspects. , 2000, Journal of andrology.

[40] J P Bonde,et al. Computer-assisted semen analysis parameters as predictors for fertility of men from the general population. The Danish First Pregnancy Planner Study Team. , 2000, Human reproduction.

[41] A. Travis,et al. Regulation of human sperm capacitation by a cholesterol efflux-stimulated signal transduction pathway leading to protein kinase A-mediated up-regulation of protein tyrosine phosphorylation. , 1999, Molecular human reproduction.

[42] D. D. de Kretser,et al. COMMENTARY Infertility in Men: Recent Advances and Continuing Controversies* , 1999 .

[43] S. Mortimer,et al. The development of smoothing-independent kinematic measures of capacitating human sperm movement. , 1999, Human reproduction.

[44] V. Kay,et al. Hyperactivated motility of human spermatozoa: a review of physiological function and application in assisted reproduction. , 1998, Human reproduction update.

[45] A. Makler,et al. Dynamic aspects concerned with the mechanism of separating motile sperm from nonmotile sperm, leukocytes, and debris with the use of high-density Percoll gradients. , 1998, Fertility and sterility.

[46] S. Mortimer,et al. Effect of seminal plasma on capacitation and hyperactivation in human spermatozoa. , 1998, Human reproduction.

[47] J A McNally,et al. In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome. , 1998, Fertility and sterility.

[48] K. Bennett,et al. A support vector machine approach to decision trees , 1998, 1998 IEEE International Joint Conference on Neural Networks Proceedings. IEEE World Congress on Computational Intelligence (Cat. No.98CH36227).

[49] S. Mortimer,et al. A critical review of the physiological importance and analysis of sperm movement in mammals. , 1997, Human reproduction update.

[50] S. Mortimer,et al. Variable kinematics of capacitating human spermatozoa. , 1995, Human reproduction.

[51] R. Aitken,et al. Definition of the optimal criteria for identifying hyperactivated human spermatozoa at 25 Hz using in-vitro fertilization as a functional end-point. , 1995, Human reproduction.

[52] G. Kopf,et al. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. , 1995, Development.

[53] S. Mortimer,et al. Andrology: Kinematics of capacitating human spermatozoa analysed at 60 Hz , 1995 .

[54] T. Ord,et al. Movement characteristics of human epididymal sperm used for fertilization of human oocytes in vitro , 1992, Fertility and sterility.

[55] G. Clarke,et al. Relationship between sperm motility assessed with the Hamilton-Thorn motility analyzer and fertilization rates in vitro. , 1991, Journal of andrology.

[56] A. Spira,et al. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). , 1991, Human reproduction.

[57] L J Burkman,et al. Discrimination between nonhyperactivated and classical hyperactivated motility patterns in human spermatozoa using computerized analysis. , 1991, Fertility and sterility.

[58] S. Mortimer,et al. Kinematics of human spermatozoa incubated under capacitating conditions. , 1990, Journal of andrology.

[59] P. Olds‐Clarke,et al. Sperm from tw32/+ mice: capacitation is normal, but hyperactivation is premature and nonhyperactivated sperm are slow. , 1989, Developmental biology.

[60] D. Wolf,et al. Temporal changes in motility parameters related to acrosomal status: identification and characterization of populations of hyperactivated human sperm. , 1988, Biology of reproduction.