@article {145, title = {Generation of sequence-based data for pedigree-segregating Mendelian or Complex traits.}, journal = {Bioinformatics}, volume = {31}, year = {2015}, month = {2015 Nov 15}, pages = {3706-8}, abstract = {

MOTIVATION: There is great interest in analyzing next generation sequence data that has been generated for pedigrees. However, unlike for population-based data there are only a limited number of rare variant methods to analyze pedigree data. One limitation is the ability to evaluate type I and II errors for family-based methods, due to lack of software that can simulate realistic sequence data for pedigrees.

SUMMARY: We developed RarePedSim (Rare-variant Pedigree-based Simulator), a program to simulate region/gene-level genotype and phenotype data for complex and Mendelian traits for any given pedigree structure. Using a genetic model, sequence variant data can be generated either conditionally or unconditionally on pedigree members{\textquoteright} qualitative or quantitative phenotypes. Additionally, qualitative or quantitative traits can be generated conditional on variant data. Sequence data can either be simulated using realistic population demographic models or obtained from sequence-based studies. Variant sites can be annotated with positions, allele frequencies and functionality. For rare variants, RarePedSim is the only program that can efficiently generate both genotypes and phenotypes, regardless of pedigree structure. Data generated by RarePedSim are in standard Linkage file (.ped) and Variant Call (.vcf) formats, ready to be used for a variety of purposes, including evaluation of type I error and power, for association methods including mixed models and linkage analysis methods.

AVAILABILITY AND IMPLEMENTATION: bioinformatics.org/simped/rare

CONTACT: sleal@bcm.edu.

}, keywords = {Base Sequence, Chromosome Segregation, Humans, Pedigree, Quantitative Trait, Heritable, Sequence Analysis, Software}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btv412}, author = {Li, Biao and Wang, Gao T and Leal, Suzanne M} } @article {321, title = {SimRare: a program to generate and analyze sequence-based data for association studies of quantitative and qualitative traits.}, journal = {Bioinformatics}, volume = {28}, year = {2012}, month = {2012 Oct 15}, pages = {2703-4}, abstract = {

MOTIVATION: Currently, there is great interest in detecting complex trait rare variant associations using next-generation sequence data. On a monthly basis, new rare variant association methods are published. It is difficult to evaluate these methods because there is no standard to generate data and often comparisons are biased. In order to fairly compare rare variant association methods, it is necessary to generate data using realistic population demographic and phenotypic models.

RESULT: SimRare is an interactive program that integrates generation of rare variant genotype/phenotype data and evaluation of association methods using a unified platform. Variant data are generated for gene regions using forward-time simulation that incorporates realistic population demographic and evolutionary scenarios. Phenotype data can be obtained for both case-control and quantitative traits. SimRare has a user-friendly interface that allows for easy entry of genetic and phenotypic parameters. Novel rare variant association methods implemented in R can also be imported into SimRare, to evaluate their performance and compare results, e.g. power and Type I error, with other currently available methods both numerically and graphically.

}, keywords = {Genetic Association Studies, Genetic Variation, Humans, Phenotype, Quantitative Trait, Heritable, Software}, issn = {1367-4811}, doi = {10.1093/bioinformatics/bts499}, author = {Li, Biao and Wang, Gao and Leal, Suzanne M} }