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 — mlnr [2016/04/13 18:02] (current) Line 1: Line 1: + ===== Linear Model Quantitative Traits ===== + Simulation of quantitative trait (QT) values follows from a simple linear model of the additive effect of mutations. A mutation contributes to the change in mean of QT value by a specific amount. For protective variants, mutations decrease QT; for detrimental variants, mutations increase QT. Under this model both analytic and empirical power and sample size calculations are available for quantitative traits analysis methods. + + ==== Command Interface ==== + + spower LNR -h + ​\\ + ​ + usage: spower LNR [-h] [-a MULTIPLIER] [-b MULTIPLIER] [-A MULTIPLIER] + [-B MULTIPLIER] [-c MULTIPLIER] [-d MULTIPLIER] + [--def_rare P] [--def_neutral VALUE VALUE] + [--def_protective VALUE VALUE] [-P P] [-Q P] + [--sample_size N] [--def_valid_locus VALUE VALUE] + [--rare_only] [--missing_as_wt] [--missing_low_maf P] + [--missing_sites P] [--missing_sites_deleterious P] + [--missing_sites_protective P] [--missing_sites_neutral P] + [--missing_sites_synonymous P] [--missing_calls P] + [--missing_calls_deleterious P] + [--missing_calls_protective P] [--missing_calls_neutral P] + [--missing_calls_synonymous P] [--error_calls P] + [--error_calls_deleterious P] [--error_calls_protective P] + [--error_calls_neutral P] [--error_calls_synonymous P] + [--power P] [-r N] [--alpha ALPHA] [--moi {A,D,R,M}] + [--resampling] [-l N] [-o file] [-t NAME] [-v {0,1,2,3}] + [-s N] [-j N] [-m METHODS [METHODS ...]] + [--discard_samples [EXPR [EXPR ...]]] + [--discard_variants [EXPR [EXPR ...]]] + DATA + ​ + positional arguments: + DATA                  name of input data or prefix of input data bundle (see + the documentation for details) + ​ + optional arguments: + -h, --help ​           show this help message and exit + ​ + model parameters: + -a MULTIPLIER, --meanshift_rare_detrimental MULTIPLIER + mean shift in quantitative value w.r.t standard + deviation due to detrimental rare variants i.e., by + "​MULTIPLIER * sigma" (default set to 0.0) + -b MULTIPLIER, --meanshift_rare_protective MULTIPLIER + mean shift in quantitative value w.r.t. standard + deviation due to protective rare variants i.e., by + "​MULTIPLIER * sigma" (default set to 0.0) + -A MULTIPLIER, --meanshiftmax_rare_detrimental MULTIPLIER + maximum mean shift in quantitative value w.r.t + standard deviation due to detrimental rare variants + i.e., by "​MULTIPLIER * sigma",​ applicable to variable + effects model (default set to None) + -B MULTIPLIER, --meanshiftmax_rare_protective MULTIPLIER + maximum mean shift in quantitative value w.r.t + standard deviation due to protective rare variants + i.e., by "​MULTIPLIER * sigma",​ applicable to variable + effects model (default set to None) + -c MULTIPLIER, --meanshift_common_detrimental MULTIPLIER + mean shift in quantitative value w.r.t standard + deviation due to detrimental common variants i.e., by + "​MULTIPLIER * sigma" (default set to 0.0) + -d MULTIPLIER, --meanshift_common_protective MULTIPLIER + mean shift in quantitative value w.r.t standard + deviation due to protective common variants i.e., by + "​MULTIPLIER * sigma" (default set to 0.0) + --moi {A,​D,​R,​M} ​      mode of inheritance:​ "​A",​ additive (default); "​D",​ + dominant; "​R",​ recessive; "​M",​ multiplicative (does + not apply to quantitative traits model) + --resampling ​         directly draw sample genotypes from given haplotype + pools (sample genotypes will be simulated on the fly + if haplotype pools are not available) + ​ + variants functionality:​ + --def_rare P          definition of rare variants: variant having "MAF <= + frequency"​ will be considered a "​rare"​ variant; the + opposite set is considered "​common"​ (default set to + 0.01) + --def_neutral VALUE VALUE + annotation value cut-offs that defines a variant to be + "​neutral"​ (e.g. synonymous, non-coding etc. that will + not contribute to any phenotype); any variant with + "​function_score"​ X falling in this range will be + considered neutral (default set to None) + --def_protective VALUE VALUE + annotation value cut-offs that defines a variant to be + "​protective"​ (i.e., decrease disease risk or decrease + quantitative traits value); any variant with + "​function_score"​ X falling in this range will be + considered protective (default set to None) + -P P, --proportion_detrimental P + proportion of deleterious variants associated with the + trait of interest, i.e., the random set of the rest (1 + - p) x 100% deleterious variants are non-causal: they + do not contribute to the phenotype in simulations yet + will present as noise in analysis (default set to + None) + -Q P, --proportion_protective P + proportion of protective variants associated with the + trait of interest, i.e., the random set of the rest (1 + - p) x 100% protective variants are non-causal: they + do not contribute to the phenotype in simulations yet + will present as noise in analysis (default set to + None) + ​ + sample population: + --sample_size N       total sample size + ​ + quality control: + --def_valid_locus VALUE VALUE + upper and lower bounds of variant counts that defines + if a locus is "​valid",​ i.e., locus having number of + variants falling out of this range will be ignored + from power calculation (default set to None) + --rare_only ​          ​remove from analysis common variant sites in the + population, i.e., those in the haplotype pool having + MAF > \$def_rare + --missing_as_wt ​      label missing genotype calls as wildtype genotypes + ​ + sequencing / genotyping artifact: + --missing_low_maf P   ​variant sites having population MAF < P are set to + missing + --missing_sites P     ​proportion of missing variant sites + --missing_sites_deleterious P + proportion of missing deleterious sites + --missing_sites_protective P + proportion of missing protective sites + --missing_sites_neutral P + proportion of missing neutral sites + --missing_sites_synonymous P + proportion of missing synonymous sites + --missing_calls P     ​proportion of missing genotype calls + --missing_calls_deleterious P + proportion of missing genotype calls at deleterious + sites + --missing_calls_protective P + proportion of missing genotype calls at protective + sites + --missing_calls_neutral P + proportion of missing genotype calls at neutral sites + --missing_calls_synonymous P + proportion of missing genotype calls at synonymous + sites + --error_calls P       ​proportion of error genotype calls + --error_calls_deleterious P + proportion of error genotype calls at deleterious + sites + --error_calls_protective P + proportion of error genotype calls at protective sites + --error_calls_neutral P + proportion of error genotype calls at neutral sites + --error_calls_synonymous P + proportion of error genotype calls at synonymous sites + ​ + power calculation:​ + --power P             power for which total sample size is calculated (this + option is mutually exclusive with option '-- + sample_size'​) + -r N, --replicates N  number of replicates for power evaluation (default set + to 1) + --alpha ALPHA         ​significance level at which power will be evaluated + (default set to 0.05) + ​ + input/​output specifications:​ + -l N, --limit N       if specified, will limit calculations to the first N + groups in data (default set to None) + -o file, --output file + output filename + ​ + runtime options: + -t NAME, --title NAME + unique identifier of a single command run (default to + output filename prefix) + -v {0,1,2,3}, --verbosity {0,1,2,3} + verbosity level: 0 for absolutely quiet, 1 for less + verbose, 2 for verbose, 3 for more debug information + (default set to 2) + -s N, --seed N        seed for random number generator, 0 for random seed + (default set to 0) + -j N, --jobs N        number of CPUs to use when multiple replicates are + required via "​-r"​ option (default set to 2) + ​ + association tests: + -m METHODS [METHODS ...], --methods METHODS [METHODS ...] + Method of one or more association tests. Parameters + for each method should be specified together as a + quoted long argument (e.g. --methods "m --alternative + 2" "m1 --permute 1000"​),​ although the common method + parameters can be specified separately, as long as + they do not conflict with command arguments. (e.g. + --methods m1 m2 -p 1000 is equivalent to --methods "m1 + -p 1000" "m2 -p 1000"​.). You can use command '​spower + show tests' for a list of association tests, and + '​spower show test TST' for details about a test. + ​ + samples and genotypes filtering: + --discard_samples [EXPR [EXPR ...]] + Discard samples that match specified conditions within + each test group. Currently only expressions in the + form of "​%(NA)>​p"​ is provided to remove samples that + have more 100*p percent of missing values. + --discard_variants [EXPR [EXPR ...]] + Discard variant sites based on specified conditions + within each test group. Currently only expressions in + the form of '​%(NA)>​p'​ is provided to remove variant + sites that have more than 100*p percent of missing + genotypes. Note that this filter will be applied after + "​--discard_samples"​ is applied, if the latter also is + specified. + ​\\ + ==== Details ==== + Model specific options are documented in details below. You should find the rest of the options [[http://​bioinformatics.org/​spower/​options|otherwise documented]]. + + === -a/​b/​c/​d/​A/​B === + These options specify the effect of quantitative trait loci in the region of interest, modeled by the shift in mean QT value due to these mutations. The unit of mean shift is the standard deviation. For example ''​-a 0.1''​ means a detrimental mutation increase the mean value of the QT by $0.1\sigma$. ''​-a''​ is QT shift due to detrimental rare variants. When used by itself, all detrimental rare variants will be assigned a fixed effect size as specified. With the ''​-A''​ option, they together model "​variable effects"​ with ''​-a''​ being the minimum effect size and ''​-A''​ being the maximum effect size for detrimental rare variants. In variable effects model the maximum effect will be assigned to the variant having smallest MAF, and the minimum effect to the one having largest MAF. Values in between are interpolated based on these specified max. and min. values. Similarly ''​-b''​ and ''​-B''​ are for fixed and variable effects of protective variants, which decrease the mean QT as oppose to increasing it. ''​-c''​ and ''​-d''​ are effects for common detrimental and protective variants respectively. No variable effects model for common variants is available for this model. + + ​ + We recommend using values ranging from 0.1 to 4.0 for rare variants. For example In the context of a trait such as human height, $0.25\sigma$ would correspond to a change in mean height of 0.5 inch. + ​ + ==== Examples ==== + *  [[http://​bioinformatics.org/​spower/​analytic-tutorial|Analytic power analysis]] for quantitative traits + *  [[http://​bioinformatics.org/​spower/​empirical-tutorial|Empirical power analysis]] for quantitative traits