MImapqtl

NAME

MImapqtl - Multiple Interval mapping module

SYNOPSIS

MImapqtl [ -o output ] [ -i input ] [ -m mapfile ] [ -E inputmodel ] [ -O outputmodel ] [ -t trait ] [ -q QTL ] [ -k Epi ] [ -d walk ] [ -S stop ] [ -L threshold ] [ -I workcode ] [ -p phase ]

DESCRIPTION

MImapqtl uses multiple interval mapping to map quantitative trait loci to a map of molecular markers. It requires a molecular map that could be a random one produced by Rmap, or a real one in the same format as the output of Rmap. The sample could be a randomly generated one from Rcross or a real one in the same format as the output of Rcross. In addition, the program can use an initial genetic model. This model will most likely be produced by running Eqtl on the results of a Zmapqtl run, but could be the results of a prior run of MImapqtl.

OPTIONS

See QTLcart(1) for more information on the global options -h for help, -A for automatic, -V for non-Verbose -W path for a working directory, -R file to specify a resource file, -e to specify the log file, -s to specify a seed for the random number generator and -X stem to specify a filename stem. The options below are specific to this program.

If you use this program without specifying any options, then you will get into a menu that allows you to set them interactively.

-o: This requires a filename for output. MImapqtl will append the file if it exists, and create a new file if it does not. If not used, then MImapqtl will use qtlcart.mim.
-i: This requires an input filename. This file must exist. It should be in the same format as the output of Rcross. The default file is qtlcart.cro.
-m: MImapqtl requires a genetic linkage map. This option requires the name of a file containing the map. It should be in the same format that Rmap outputs. The default file is qtlcart.map.
-t: Use this to specify which trait MImapqtl will analyze. If this number is greater than the number of traits, then all traits will be analyzed unless the trait name begins with a minus sign. If a negative number is given, then only traits beginning with a plus sign will be analyzed. The default is to analyze trait 1 only.
-E: Allows the user to specify the name of the file containing the genetic model for input. This file should be in the format of Rqtl.out and produced by Rqtl, Eqtl or MImapqtl. A new model will be placed in the file specified with the -O option. For an initial analysis (phase 0), this will default to qtlcarti.mqt.
-O: Allows the user to specify the name of the file containing the genetic model for output. For an initial analysis (phase 0), this will default to qtlcarto.mqt.
-q: MImapqtl has a limit to the number of QTL it can analyze. For 32 bit machines, this is 19 QTL. For 64 bit machines, this can be 31. If you set this to a number higher than that allowed, it will be reset to the maximum allowed for the machine type.
-k: The user can specify the maximum number of epistatic terms allowed in the model.
-d: MImapqtl walks along an interval at this rate during the refinement of QTL positions and the search for more QTL.
-S: Requires an integer value to indicate the information criterion for declaring the presence or absence of a parameter. Information criteria are explained below.
-L: Requires a real value to indicate the threshold for adding or deleting parameters to a model. Comparisons are made based on the information criterion function specified with the -S option above. The default is 3.84. If this is set too low, the program will continue to find QTL until it hits the upper limit. If set too high, it will not find any QTL.
-I: Requires an eight character string that codes for what the program should do. See below for more explanation.
-p: is used with an integer to specify the phase of the analysis. See below for more explanation.

FILES

You will need a map of molecular markers, qtlcart.map and a data set, qtlcart.cro. You can also specify an initial genetic model, qtlcart.qtl.

The input format of the molecular map should be the same as that of the output format from the program Rmap. The input format of the individual data should be the same as the output format of the program Rcross. If you use an initial genetic model, it should be of the same format as an Rqtl output file. The output of Eqtl will also have such a model, as will the output of MImapqtl itself.

MImapqtl can produce three types of output files. Most results will be put in the qtlcart.mim file, while the Rqtl formatted output file will be qtlcart.mqt. If you choose to calculate residuals, they will be placed in qtlcart.res, which will have the same format as an Rcross output file.

NOTES

ANALYSIS

If MImapqtl is invoked and an initial model is provided, it will do the following seven steps:

Step 1.: Initial Model; Read in the initial model and convert it to a usable format. The model is read from the file specified by the -E option and must exist.
Step 2.: Parameter Estimation; Estimate all parameters in the initial model. If used, then the initial model simply specifies the positions of the QTL.
Step 3.: Refine Positions; Refine the estimates of the positions of all QTL in the initial model. This refinement occurs in the interval where the QTL resides. This is not an option to search other intervals for QTL.
Step 4.: Test parameters; Test each parameter in the initial model for significance. This follows a backward elimination procedure, and those parameters that do not lead to a significant improvement in fit are dropped. The threshold for dropping parameters is specified by the -L option. The information criterion is calculated for the model with and without the tested parameter, and the difference must be greater than the threshold for the effect to be retained.
Step 5.: Search for QTL; Search for more QTL. This follows a forward stepwise procedure, whereby the genome is scanned, the most likely place for a new QTL is determined, and if it results in a significant improvement, is retained.
Step 6.: Epistasis search; Search for epistatic interactions between the QTL in the model. This will do all pairwise combinations of the QTL that survive steps 4 and 5.
Step 7.: Calculate predictions; Calculate breeding values, the Variance-Covariance matrix and R2 values for the parameters.

If the user specifies that no initial model is to be used, then the analysis starts with step 5 above.

WORK CODE

The Work Code must be specified with an 8 letter string. Each letter in the string is a flag to tell the program whether to do a certain step. Some of the flags have options to modify the behavior of that step. The 8 letter string starts from position 0. The remaining positions (1-7) correspond to the steps given in the previous section.

Position 0.: Scan flag; This can take on values S or s. If S, then MImapqtl will go into scan mode. It will do one pass in the search for QTL phase, and print out positions and a likelihood profile to the output file. The user can then plot the values and decide where to place a new QTL.
Position 1.: Model flag; Tells MImapqtl whether to use the initial model specified with the -E option. If M, then use the model, and if m, don't use it. If you use m, then you should also specify prt in positions 2, 3 and 4. For example, smprtSEC would make sense: It would search for QTL de novo.
Position 2.: Parameter flag; Use a P here if you want MImapqtl to re-estimate the paramters in the initial model. Use a p if you want to skip this step. The case of this position should almost always match that of position 1.
Position 3.: Refine postion flag; Use an R here if you want MImapqtl to refine the position estimates in the initial model. Use an r if you want to skip this step. If you don't have an initial model, then this should be r. You can also extend the refinement of position to the immediate adjacent intervals by using A in this position.
Position 4.: Test flag; Use a T here if you want MImapqtl to test the significance of the parameters in the initial model. Use a t if you want to skip this step. If you don't have an initial model, then this should be t. You can use D in place of T in order to test dominance effects only, but t his is only relevant with three marker classes. Finally, if you want to test any existing epistatic interactions, then use E.
Position 5.: Search flag; Use an S here if you want MImapqtl to search for more QTL. Use an s if you want to skip this step. You can also specify a A if you only want to search for the additive effects of putative QTL (that is, don't search for dominance effects in Fx lines). Finally, if you use a D here, MImapqtl will only search for dominance effects at QTL locations that don't already have them.
Position 6.: Epistasis flag; Use an E here if you want MImapqtl to search for epistatic effects. Use an e if you want to skip this step. By default, the MImapqtl does a forward stepwise search for epistatic terms. If you want to try a backward elimination approach, use a B in this position, but be aware that if there are too many epistatic terms, the request will be ignored in favor of a forward search. Finally, a U in this postion will do a backward elimination approach but the limit to the number of parameters will be the sample size minus one.
Position 7.: Covariance flag; Use a C here if you want MImapqtl to calculate the variance-covariance matrix, R2 values and breeding values for the final model. Use a c if you want to skip this step. If you specify an R in this spot, then for the current model, the residuals for the trait being analyzed are calculated and used as the new trait values. These residuals are written to a file stem.res where stem is the filename stem.

The default string is smprtSeC, which tells MImapqtl to scan for QTL without an initial model, where the the additive and dominance effects are treated as a unit.

INFORMATION CRITERIA

See Kao, Zeng and Basten (1999) for more detailed information on the information criteria. We use

        IC(k) = -2(log(L) - k c(n) / 2)

where L is the likelihood for a k-parameter model and log is the natural log function. The penalty function c(n) takes one of six forms:

1. c(n) = log(n)
2. c(n) = 2
3. c(n) = 2 log(log(n))
4. c(n) = 2 log(n)
5. c(n) = 3 log(n)
6. c(n) = 0

Use the numbers above with the -S option to indicate which information criterion you want to use. If you use penalty functions 1 through 5 above, then you should also specify a threshold of 0.0 with the -L function. Penalty function 6 is equivalent to no penalty function and requires an experimentwise threshold value that might be obtained via a permutation test.

ANALYSIS PHASE

MImapqtl can read a genetic model and proced with various tasks as explained above. This leads to the idea of repeating the analysis with the results of a previous run of the program. One can think of doing the analysis in steps or phases. The default is to set the phase to zero. If the phase is set to zero, then the default input file for a genetic model is qtlcart.eqt, the output is qtlcart.mqt and the general output file is qtlcart.mim. At the end of the analysis, the phase remains 0.

If one sets the phase to a positive integer (generally starting with 1), then the default input is to assume that input and output files follow a rule. Assume the filename stem is qtlcart and the phase is i. The input genetic model will be set to qtlcartPhasei-1.mqt, the output genetic model will be written to qtlcartPhasei.mqt, and the general output file will be qtlcartPhasei.mim. At the end of the analysis, the phase variable i will be incremented by one and recorded in the qtlcart.rc file. This makes it easier for the program (and the user) to keep track of previous and current results. Also note that if you used an R in position 7 of the workcode, then the output file containing a new dataset with the residuals replacing the trait values will be put in qtlcartPhasei.res.

EXAMPLES

        % MImapqtl -I smprtSeC

Calculates the best model for the dataset in qtlcart.cro using the map in qtlcart.map and the model in qtlcart.eqt, but only searches for main effects (additive and dominance).

Here is a sequence using the example dataset mletest.cro along with its map file mletest.map, both of which come with the programs. Assume that these two files have been placed in an empty subdirectory which is now the current working directory.

        % MImapqtl -A -V -I smprtSeC  -L 0.0 -S 1 -p 1 -X mletest &
        % MImapqtl -A -V -I sMPrTseC    &
        % MImapqtl -A -V -I sMPRtseC    &
        % MImapqtl -A -V -I sMPrtSeC    &
        % MImapqtl -A -V -I sMPrtsBC    &

The first invocation sets the filename stem, the information criterion and threshold for adding parameters and indicates that it is phase 1. The -I option tells MImapqtl to search for additive QTL. The second invocation tests each QTL found in the first phase. The third step refines the positions of all remaining QTL. The fourth step searches for more QTL (and probably won't find any). The fifth step searches for interactions between the identified putative QTL. The phase variable is updated after each step, so MImapqtl knows where to find the results from the previous step.

REFERENCES

Biometrics

Theoret. Pop. Biol.

Genetics

152

Genetical Research, Camb.

CAVEATS

We are still doing some simulations to determine the best information criterion to use. At present, the defaut of 1 with a threshold of 0.0 seems to work well for a variety of data sets. If the defaut detects no QTL, then you might try information criteria 2, 3 or 6.

BUGS

Still under development: We hope to add the joint analysis of multiple traits in multiple environments. We are also working on the output formats.

The A option for refining positions in the work code does not yet behave correctly. It tends to place all putative QTL at the left flanking marker of an interval. If you use this option, then re-run MImapqtl with an R in position four to better refine the position estimate of the QTL.

CONTACT INFO

In general, it is best to contact us via email (basten@statgen.ncsu.edu)

        Christopher J. Basten, B. S. Weir and Z.-B. Zeng
        Bioinformatics Research Center, North Carolina State University
        1523 Partners II Building/840 Main Campus Drive
        Raleigh, NC 27695-7566     USA
        Phone: (919)515-1934

Please report all bugs via email to qtlcart-bug@statgen.ncsu.edu.

The QTL Cartographer web site ( http://statgen.ncsu.edu/qtlcart ) has links to the manual, man pages, ftp server and supplemental materials.

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