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Extreme Quantitative Traits Model

Under this model, extreme quantitative traits are simulated based on given percentile upper (\(p\)) and lower (\(q\)) bounds. There are two approaches to generate extreme QT values:

  • Finite sample pool method: QT values are generated from simulation in ''LNR'' model; only samples having QT larger than \(p^{th}\) upper percentile or smaller than \(q^{th}\) lower percentile are kept.
  • Infinite sample pool method: QT values are generated from truncated standard normal distribution following probability density function \(f(x)\propto \phi(x)I_{\Phi^{-1}(x)\in(p, q)}(x)\)

In SEQPower no specific statistical methods for analyzing extreme quantitative traits are implemented. To analyze data from this model, one can use methods for regular QT analysis with permutation testing to obtain p-value estimate, or implement via ''RTest'' interface some more sophisticated analysis methods.

Command Interface

spower ELNR -h


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usage: spower ELNR [-h] [-a MULTIPLIER] [-b MULTIPLIER] [-A MULTIPLIER]
                   [-B MULTIPLIER] [-c MULTIPLIER] [-d MULTIPLIER]
                   [--QT_thresholds C C] [--sample_size N] [--p1 P]
                   [--def_rare P] [--def_neutral VALUE VALUE]
                   [--def_protective VALUE VALUE] [-P P] [-Q P]
                   [--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)
  --QT_thresholds C C   lower/uppwer percentile cutoffs for quantitative
                        traits in extreme QT sampling, default to "0.5 0.5"
  --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 avaliable)

sample population:
  --sample_size N       total sample size
  --p1 P                proportion of affected individuals (default set to
                        0.5), or individuals with high extreme QT values
                        sampled from infinite population (default set to None,
                        meaning to sample from finite population speficied by
                        --sample_size option).

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)

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 similar to options in ''LNR'' model. General simulation and analysis options are otherwise documented. The infinite sample pool method is triggered by --p1 option. If --p1 is not specified, the finite sample pool method will be used.

--QT_thresholds

This option takes two values, the lower and upper QT percentile cutoff which defines case control status. QT values under the lower cutoff are considered controls; QT values higher than the upper cutoff are considered cases.

Examples