Incorporation of DNA Tests into a Genetic Evaluation
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Incorporation of DNA Tests into a Genetic Evaluation Incorporation of DNA Tests into a Genetic Evaluation Presentation Transcript

  • Incorporation of DNA Tests Introduction Tenderness Incorporation of DNA Tests into a Genetic Example Accuracies Evaluation Interim EPDs Implementation Stephen D. Kachman Department of Statistics University of Nebraska–Lincoln 1 / 43
  • Introduction Incorporation of DNA Tests Introduction Objective is to evaluate the genetic potential of an animal Tenderness Example Phenotypic information Accuracies Pedigree information Interim EPDs Implementation 2 / 43
  • Introduction Incorporation of DNA Tests Introduction Objective is to evaluate the genetic potential of an animal Tenderness Example Phenotypic information Accuracies Pedigree information Interim EPDs Incorporate DNA information Implementation Marker Information Molecular Breeding Values 2 / 43
  • Introduction Incorporation of DNA Tests Introduction Objective is to evaluate the genetic potential of an animal Tenderness Example Phenotypic information Accuracies Pedigree information Interim EPDs Incorporate DNA information Implementation Marker Information Molecular Breeding Values Implementation Fit alongside current approaches Practical Flexible 2 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Accuracies Fostered by the NBCEC Interim EPDs Team Implementation Rohan Fernando (Iowa State) Rob Tempelman (Michigan State) 3 / 43
  • Outline Incorporation of DNA Tests Introduction Quick overview of current approach to genetic evaluation Tenderness Example DNA marker information Accuracies Incorporation into genetic evaluations Interim EPDs MBVs as correlated traits Implementation Similarities and differences with other correlated traits Challenges and how to address them Initial analysis Some implications Where do we go from here? 4 / 43
  • Current Phenotypic Based Analysis Incorporation of DNA Tests Sources of information: Phenotypic records on the trait of interest Introduction Phenotypic records on correlated traits Tenderness Pedigree information Example Evaluation Accuracies Best Linear Unbiased Prediction Interim EPDs Implementation Phenotypic Data BLUP EPD Pedigree Information 5 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Overall this approach works well Accuracies Phenotypic data may be limited Interim EPDs Difficult to collect Implementation For example: Carcass traits Need complementary sources of information DNA Information Summarized into MBVs or Marker Scores 6 / 43
  • Incorporation of DNA Tests Introduction Tenderness DNA Information Example Single marker Accuracies Several markers Interim EPDs Implementation 7 / 43
  • Incorporation of DNA Tests Introduction Tenderness DNA Information Example Single marker Accuracies Several markers Interim EPDs Thousands of markers Implementation Sequence data 7 / 43
  • Incorporation of DNA Tests Introduction Tenderness DNA Information Example Single marker Accuracies Several markers Interim EPDs Thousands of markers Implementation Sequence data Summarized into marker scores Estimated from reference populations Flexibility to handle evolving molecular technology Flexibility to handle evolving statistical methodology 7 / 43
  • Marker Scores and Phenotypes Incorporation of DNA Tests Introduction Tenderness Example Marker Marker Accuracies Genotype Score Interim EPDs Implementation Breeding DNA Genotype Phenotype Value Environment 8 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Conceptually marker scores can be viewed as a correlated Accuracies trait Interim EPDs Similar to using Birth Weight when evaluating Calving Implementation Ease Observable trait Underlying genetic component which is correlated to the trait of interest 9 / 43
  • Tenderness Example Incorporation of DNA Tests Introduction Tenderness Warner-Bratzler Shear Force (kg) Example Phenotype Only Model 410 steers Full Model Marker Only Model 14 sires Reduced Models 36 contemporary groups Accuracies Interim EPDs Marker scores Implementation Pfizer GeneSTAR Tenderness Igenity Tenderness MMI Tru-Tenderness 10 / 43
  • Models Incorporation of DNA Tests Phenotypic Model (Single Trait Model) Introduction Only include phenotypic data Tenderness Fixed: Contemporary group Example Phenotype Only Random: Direct additive effect Model Full Model Residual Marker Only Model Reduced Models Accuracies Interim EPDs Implementation 11 / 43
  • Models Incorporation of DNA Tests Phenotypic Model (Single Trait Model) Introduction Only include phenotypic data Tenderness Fixed: Contemporary group Example Phenotype Only Random: Direct additive effect Model Full Model Residual Marker Only Model Reduced Models Marker Model (Three Trait Model) Accuracies Fixed: Company baseline effect Interim EPDs Random: Direct additive effect Implementation 11 / 43
  • Models Incorporation of DNA Tests Phenotypic Model (Single Trait Model) Introduction Only include phenotypic data Tenderness Fixed: Contemporary group Example Phenotype Only Random: Direct additive effect Model Full Model Residual Marker Only Model Reduced Models Marker Model (Three Trait Model) Accuracies Fixed: Company baseline effect Interim EPDs Random: Direct additive effect Implementation Full Model (Four Trait Model) 11 / 43
  • Models Incorporation of DNA Tests Phenotypic Model (Single Trait Model) Introduction Only include phenotypic data Tenderness Fixed: Contemporary group Example Phenotype Only Random: Direct additive effect Model Full Model Residual Marker Only Model Reduced Models Marker Model (Three Trait Model) Accuracies Fixed: Company baseline effect Interim EPDs Random: Direct additive effect Implementation Full Model (Four Trait Model) Reduced Models Use all available phenotypic and marker scores Exploit commonalities in the genetic basis of the marker scores 11 / 43
  • Phenotypic Accuracies Incorporation of DNA Tests Introduction Tenderness Example Phenotype Only Generation Median Range Model Full Model Sire 0.30 0.00–0.39 Marker Only Model Progeny 0.21 0.00–0.24 Reduced Models Accuracies Interim EPDs Accuracies are greater in the sires compared to the Implementation progeny. 12 / 43
  • Full Model Incorporation of DNA Tests Introduction Included four traits Tenderness Shear Force Example Phenotype Only Company A Marker Score Model Full Model Company B Marker Score Marker Only Model Company C Marker Score Reduced Models Accuracies Genetic variances for the shear force and marker scores Interim EPDs Genetic Correlations of shear force with each of the marker Implementation scores Genetic correlations between the marker scores No residual variation in the marker score 13 / 43
  • Median Accuracies Incorporation of DNA Tests Introduction Tenderness Example Model Phenotype Only Model Generation Phenotypic Full Full Model Marker Only Sire 0.30 0.34 Model Reduced Models Progeny 0.21 0.30 Accuracies Interim EPDs Implementation Accuracy increases with the addition of marker information Benefit is greatest for the individual who is genotyped 14 / 43
  • Full versus Phenotype EPDs (r=0.90) Incorporation of DNA Tests Sire EPD Introduction 0.3 q Tenderness Example 0.2 Phenotype Only Phenotype Based EPD Model Full Model 0.1 Marker Only q q Model q q Reduced Models qq 0.0 q q Accuracies q q −0.3 −0.2 −0.1 Interim EPDs q Implementation q q −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Combined EPD 15 / 43
  • Full versus Phenotype EPDs (r=0.85) Incorporation of DNA Tests Progeny EPD Introduction q q Tenderness Example 0.4 q Phenotype Only Phenotype Based EPD Model q Full Model q q Marker Only q qq Model q q q qq q 0.2 qq q q q q q q q q Reduced Models q q qq q q q q qqq q q q q q q qqqqq q q q q q q qqq qq q q q q qq q q q q qq q qq Accuracies q qq q qq q q qq q q qq q q q qq q q q q q qq q qq qq q q q qq qqqqqq q qq q q q qq qq qq q qq q q q q q q q q q q q q qqqqqq q qq qq q q qq q q q q qq q qq q q q q q 0.0 Interim EPDs q q qq q q q q q q q q q qqqq q q q q q q q q qqq q qqqqq qq qq q q qq qq q qq q q qq qq qq qq q q q q q q qq q q q q q q q q q q qqq q q q qq q q q qq Implementation qq q qqqq q q qq q q q q q qqq q qq qq q qq qq q q q qq q q q q q q q q q qqq qq qqqq q q qq qq q q q q q qqq q q qq q qq q qq q qq q qq q −0.2 q q q q q q q qq q q qq q q q qq q q q q −0.2 0.0 0.2 0.4 0.6 Combined EPD 16 / 43
  • Marker only model Incorporation of DNA Tests Introduction Tenderness Example Phenotype Only Used genetic parameter estimates from the full model Model Full Model Estimation of genetic correlations between the shear force Marker Only Model and marker scores requires that both be observed in the Reduced Models same data set. Accuracies Interim EPDs Excluded all shear force data when predicting the shear Implementation force EPDs 17 / 43
  • Median Accuracies Incorporation of DNA Tests Introduction Model Tenderness Generation Phenotypic Full Marker Example Phenotype Only Model Sire 0.30 0.34 0.13 Full Model Marker Only Progeny 0.21 0.30 0.16 Model Reduced Models Accuracies Interim EPDs Marker only accuracy is greatest in the individual who is Implementation genotyped. Once an individual has been genotyped, genotyping additional relatives doesn’t have a direct impact on accuracy. 18 / 43
  • Full versus Marker EPDs (r=0.72) Incorporation of DNA Tests Sire EPD Introduction q Tenderness 0.2 Example Phenotype Only Model q Marker Based EPD Full Model q 0.1 Marker Only Model Reduced Models q q Accuracies 0.0 q q q q Interim EPDs qq Implementation −0.1 q q −0.2 q −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Combined EPD 19 / 43
  • Full versus Marker EPDs (r=0.77) Incorporation of DNA Tests Progeny EPD 0.5 Introduction q Tenderness 0.4 Example q Phenotype Only 0.3 Model q Marker Based EPD Full Model q q q q q q q Marker Only q q q 0.2 Model q q q q q q qq q q q Reduced Models q q q q q q qq q q q q q qq q q q q q q q qq qq q q 0.1 q q q qq qq q Accuracies q q q q qq q q q q q q qq q qq q q q qqq q q q q q q q q q qq q q qq q q qq q q q q qq qq qq q q qq q qq Interim EPDs q q q qq q q qq qqq q qq qqq qq qq q q qqqqq q q q q q 0.0 q q q q q q q q q q qq qq q q q q q q q q q q qq q qqq qq q qqq qqqq qq qqq q q qq q q q q q qq q q qqq q q q q q q q q Implementation qq q q qqqq q qqqq q q q q q qq q qq q q q q qq q q qq qqq q qq q q q q qqq q qq q q q qq q q q q q q q q q q qq q q q q q qqqq q q q q q q q q q qq q qq q q q qq q q q q qq q q qq q q q q q q q qq q qqq qq q q q q qq q q q qq q q −0.2 qq q qq qq q q q q q q qq q qq q qq q q q q q q −0.2 0.0 0.2 0.4 0.6 Combined EPD 20 / 43
  • Phenotypic versus Marker EPDs (r=0.40) Incorporation of DNA Tests Sire EPD Introduction q Tenderness 0.2 Example Phenotype Only Model q Marker Based EPD Full Model q 0.1 Marker Only Model Reduced Models q q Accuracies 0.0 q q q q Interim EPDs q q Implementation −0.1 q q −0.2 q −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Phenotype Based EPD 21 / 43
  • Phenotypic versus Marker EPDs (r=0.34) Incorporation of DNA Tests Progeny EPD 0.5 Introduction q Tenderness 0.4 Example q Phenotype Only 0.3 Model q Marker Based EPD Full Model q q q q q q q Marker Only q q q 0.2 Model q q Reduced Models q qq q qq q q q q q q qq qq q q q q q qqq q q q q qq q q q qq q q 0.1 Accuracies q q q qq q q q q q q qq q q qqq q q qq q q q q qq qqq q q q q q q q qqq q q q q q q q q q q q q qq qq q q q q qq q q q qqq q q qq q qqq q q qqq q q qq q q qq q Interim EPDs q q qq q q q q qq q qq q q 0.0 q q q q qq q qqqq q qq q q q qq q qq q qq qq q q q q qq qq q q q q q q q q qq q q q q qq q qq q q q qqq q q qq q q q qq q q q q q q qq q q q q Implementation q q q q qq qqqqq qqqq qq q q q q q q qq q q qqq q q q qq q q q q q q qq q q q qq q q q q qqq q q q q q qq q q q q q qqq q qqqq qqq qq q q q qq q q qq q q q q q q q q q q q q q q q q q qq q q q q q qq q q q q qq q q q q q q q q q −0.2 qq q q qq qqq q q q q q q q q q qq q q q q −0.2 0.0 0.2 0.4 Phenotype Based EPD 22 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Phenotype Only Given the actual genetic parameters Model Full Model Full model produces the BLUP of the EPD Marker Only Model Same criteria used for the current phenotypic based Reduced Models evaluations Accuracies Accuracies and Interim EPDs are available using standard Interim EPDs approaches Implementation 23 / 43
  • Need for a Reduced Model Incorporation of DNA Tests Introduction Tenderness Example A direct implementation of this approach would require a Phenotype Only Model new trait whenever a new (or modified) marker score is Full Model Marker Only introduced Model Reduced Models Increases the computational and memory requirements Accuracies Reduced models will allow for the evolution of marker Interim EPDs scores while keeping the computational and memory Implementation requirements within reason 24 / 43
  • Conceptual framework Incorporation of DNA Tests Given the common genetic basis of the marker scores it is Introduction expected that they will share a number of common Tenderness features Example Phenotype Only Partition a marker score into two independent components Model Full Model Marker Only Model Reduced Models Accuracies Interim EPDs Implementation 25 / 43
  • Conceptual framework Incorporation of DNA Tests Given the common genetic basis of the marker scores it is Introduction expected that they will share a number of common Tenderness features Example Phenotype Only Partition a marker score into two independent components Model Full Model 1 Component associated with the true EPD of the trait Marker Only Model 2 Residual component Reduced Models Accuracies Interim EPDs EPD Implementation Marker Marker = b EPD + Score Residual 25 / 43
  • EPD Component Incorporation of DNA Tests Introduction Tenderness Each marker score will have its own weight component (b) Example Phenotype Only Function of the genetic correlation between the marker Model Full Model score and the phenotypic trait. Marker Only Model Reduced Models Allows for different units between the marker score and Accuracies phenotypic trait. Interim EPDs Allows for multiple marker scores on an individual animal. Implementation Maintains the sparsity and the size of the estimating equations. 26 / 43
  • Residual Component Incorporation of DNA Tests Introduction Tenderness Example Models the proportion of variability in the true EPD not Phenotype Only Model accounted for by the marker scores. Full Model Marker Only The greater the correlation between a marker score and Model Reduced Models the EPD the smaller the residual variance. Accuracies The correlation in the residual components accounts for Interim EPDs redundant information in multiple marker scores. Implementation Allow a quantification of the gain in accuracy from using multiple marker scores. 27 / 43
  • Incorporation of DNA Tests Introduction If marker scores are only available on unrelated animals. Tenderness Example There will be only a trivial impact on the computational Phenotype Only Model requirements. Full Model Marker Only Model For related animals Reduced Models Introduces an extra trait for each marker Accuracies Interim EPDs However, because of the independence of the residual Implementation component from the effects of interest Should be possible to reduce the number traits, with a minimal impact on the estimated EPDs 28 / 43
  • Reduced Models Examined Incorporation of DNA Tests Introduction Tenderness Example Phenotype Only Because observations were collected on half-sibs the Model Full Model residual components will be correlated Marker Only Model Reduced Models Two reduced models were compared to four trait Accuracies combined model. Interim EPDs Three trait model Implementation Two trait model 29 / 43
  • Full versus Three Trait EPDs (r=0.99) Incorporation of DNA Tests Sire EPD Introduction q Tenderness 0.3 Example Phenotype Only Three Trait Approx EPD 0.2 Model Full Model Marker Only q 0.1 Model Reduced Models q q q q −0.1 0.0 Accuracies q qq q Interim EPDs q Implementation q q −0.3 q −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Combined EPD 30 / 43
  • Full versus Three Trait EPDs (r=0.99) Incorporation of DNA Tests Progeny EPD Introduction 0.6 q Tenderness q Example 0.4 Phenotype Only qq Three Trait Approx EPD Model qq Full Model q Marker Only q qq q qqq Model q 0.2 qq q qq Reduced Models qqq qq qq qq q q qq qq qq q Accuracies q qq qq qq qqqq qq qq q qqq q qq qqq qqq qqq qqq q q qqq q qq q q q q qq qqq q q qq q 0.0 Interim EPDs qqq qqq q q qqq qqqq qqq qqq qqq qq qq q q qqq qq qq qqq qq q q qq qq qq qq q qqqq qqq qqq q q Implementation qq q qq q qq q qq q qq qq qq q qq q q qq qq q q qqq qq qqqq qq qq −0.2 qqqq qqq qq qqq q qq qqq qq q q q qqqq qq q q q q q qq q −0.2 0.0 0.2 0.4 0.6 Combined EPD 31 / 43
  • Full versus Two Trait EPDs (r=0.98) Incorporation of DNA Tests Sire EPD Introduction 0.3 q Tenderness Example 0.2 q Phenotype Only Two Trait Approx EPD Model Full Model 0.1 Marker Only q q Model q Reduced Models q 0.0 q q q q Accuracies −0.1 q Interim EPDs q q Implementation −0.3 q −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Combined EPD 32 / 43
  • Full versus Two Trait EPDs (r=0.99) Incorporation of DNA Tests Progeny EPD 0.6 Introduction q Tenderness q Example q 0.4 Phenotype Only q Two Trait Approx EPD Model q q qq Full Model q qq q Marker Only q qq 0.2 Model q qqq q q qq q q q qq q q qq Reduced Models qq qqq q q q q qq q qq qq q q qqqq q q q qq q qq qq q q q q q qq q q Accuracies q qqqqq q q qqqqq qqqqqqq q qq q qqq qq q qq qqqqqqq q qqqq q q qq qq q qqq q 0.0 q qqqq q q q q q q q qqq q qqqq Interim EPDs q qqqqqq qq qqq q qqqqq qq qq qq q qq q qqqq q qq qqq qqq qq qq qq qq q qqq qqqqq q q qqq q Implementation qq q q q qq q qqqq qq qq qqqq q qq qq q q q qqq q qq q qqq q q q qqqqqq qq q −0.2 qqqq qq q qqq qq qq q q q q qq q q qqq qq q q q q q qq q −0.2 0.0 0.2 0.4 0.6 Combined EPD 33 / 43
  • Comparison with the Phenotype Model Incorporation of DNA Tests Phenotype Model Reduced Model 0.3 Sire EPD Sire EPD 0.3 q q Introduction 0.2 0.2 q Two Trait Approx EPD Phenotype Based EPD Tenderness 0.1 0.1 q q q q Example qq q q q q 0.0 q q 0.0 q q q q q Phenotype Only q −0.1 q −0.3 −0.2 −0.1 Model q q q Full Model q Marker Only −0.3 Model q q Reduced Models −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 −0.3 −0.2 −0.1 0.0 0.1 0.2 0.3 Combined EPD Combined EPD Accuracies Interim EPDs Progeny EPD Progeny EPD 0.6 Implementation q q q q q 0.4 0.4 q q Two Trait Approx EPD Phenotype Based EPD q q q qq q q q q q qq q q q q q qq q q qq 0.2 q qqq q q 0.2 qq q q qq qq q q q q q q qq q qqq qq q q qq q q qq q qq q qq q qq qqq q qq qq q q q q qqq q qq q q qqqq q q qqq q q q qq qq q q qqq q q q q q q qq q qq q q qq qq qq q q q qq q q q q q q q qqqqq q q qqqqq qq qq qqqq q qq q qq q q qq q q qq q q q qq q q q q qq q qqq qq q q q q q qq q q qq qqqqqq q qq qq qq q qq q qqqq q q qqqqq q q qq qqq q q q qqqq q 0.0 q q q q qq qq qq q q qq q q q q q q qqqqqq q qq qq qq q q q q qq q q q q q q q qqq q qqq qq qq q q q q qq q q q q q qqqqqq qq qqqq q qq 0.0 q q qq q q qq qqqq qq qq q qq q q q q qqq q q q qq q q q q qqq q qqqqq qq qq q q qq qq q q q q qqqq q q qqq q q q qqqqqqq q qq q q q qq q q q q qq qqqq q q qq qqqq qq q qq q qq q q q qq q qq q qq q qq q qqqqq qqqq qq q q q q qq q q qqq q q qq qq qq q q q q q qq q qqqq qq qq qqqq qq q qqq q qq qq q qq qq q q q qq q q q q qq q q q q qq q q q q q qqq q qq q q qq qqqqq q −0.2 q q qqq qq qqqq q q qq qq q q q q qqq qqq q q q q q qqqqq qq qq q q q q qq q qq q qq q q qq q qq q qq q qq −0.2 q q q q q q q qqq q qq qq q q qq q q q q q q qq q qq q qq q q q −0.2 0.0 0.2 0.4 0.6 −0.2 0.0 0.2 0.4 0.6 Combined EPD Combined EPD 34 / 43
  • Accuracies Incorporation of DNA Tests Introduction Calculated using a h2 of 0.4 and a genetic correlation Tenderness between the marker scores and shear force of 0.45. Example Accuracies Single Marker Score with 10 sires and 10 progeny/sire Interim EPDs Implementation Accuracy Phenotype Genotype Sire Progeny Progeny None 0.27 0.24 Progeny Progeny 0.28 0.29 Progeny Sire 0.31 0.25 Progeny Both 0.33 0.29 35 / 43
  • Without Phenotype Information Incorporation of DNA Tests Introduction Tenderness Example Accuracies Accuracy Interim EPDs Phenotype Genotype Sire Progeny Implementation None Progeny 0.07 0.11 None Sire 0.10 0.02 None Both 0.10 0.11 36 / 43
  • Single Progeny/Sire Incorporation of DNA Tests Introduction Tenderness Example Accuracy Accuracies Phenotype Genotype Sire Progeny Interim EPDs Progeny None 0.05 0.20 Implementation Progeny Progeny 0.05 0.25 Progeny Sire 0.13 0.21 Progeny Both 0.13 0.25 37 / 43
  • Without Phenotype Information Incorporation of DNA Tests Introduction Tenderness Example Accuracies Accuracy Interim EPDs Phenotype Genotype Sire Progeny Implementation None Progeny 0.02 0.10 None Sire 0.10 0.02 None Both 0.10 0.10 38 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Once an individual has been genotyped there is minimal Accuracies benefit in terms of accuracy to genotyping relatives. Interim EPDs Indirect benefit, if the genotyped ancestor has phenotypic Implementation information. Greatest benefit from genotyping is for animals with limited phenotypic information. 39 / 43
  • Interim EPDs Incorporation of DNA Tests Introduction Tenderness Simplified, an interim EPD: Example Takes the EPD from the current evaluation Accuracies Typically based on the parental EPDs Interim EPDs Implementation Along with new information Typically based on an individual’s own adjusted record deviated from the adjusted records of its contemporaries, The new information is then given a weight and added to the individual’s current EPD to produce an interim EPD. 40 / 43
  • Marker Score Interim EPDs Incorporation of DNA Tests Introduction Tenderness Example A marker score on an individual is a new piece of information Accuracies Interim EPDs Marker score would need to be adjusted in the same way a phenotypic record is adjusted Implementation Using the appropriate weight the adjusted marker score is added to the current EPD to produce a marker score interim EPD. The weight will be a function of the genetic variances and covariances. 41 / 43
  • Incorporation of DNA Tests Introduction Tenderness Example Methodology is in place. Accuracies Methodology is based on a robust and familiar statistical Interim EPDs foundation. Implementation EPDs, Accuracies, and Interim EPDs will be available Extension of the current approach to genetic evaluation. Can make use of lessons already learned 42 / 43
  • What needs to be done? Incorporation of DNA Tests Introduction Estimation of genetic parameters Tenderness Resource populations for estimation of genetic parameters Example Accuracies Reporting criteria Interim EPDs Evaluate the effect of selective reporting Implementation Criteria for determining when a marker score is ready to be included Step beyond validation Evaluate the trade off between computational requirements and model complexity Software development 43 / 43