Golden Helix PBAT Features
Pre-Study Power Calculations
The PBAT capabilities for power calculations are a software implementation of the approaches to analytical power calculations for FBATs by [Lange 2002a, Lange 2002b, Lange 2002c] . They allow you to assess the power of family-based association tests (FBATs) for a large variety of different designs:
- Dichotomous/binary and continuous traits.
- Missing parental information.
- Multiple offspring per family.
- Combinations of different family-types.
- Different genetic models.
- Different ascertainment conditions for the first and second proband.
- Marker and disease locus are not identical.
- Combination of different family-types and different ascertainment conditions.
- Verification of all power calculations by Monte-Carlo simulations.
Power calculations also allow you to assess the power of non-family-based association test designs for both case/control studies and studies based on quantitative traits.
PBAT Data Analysis
The tools which have been implemented in PBAT for the analysis of quantitative traits are discussed in a series of papers by Lange and Laird (2002) and Lange et al (2003a,b,c,d,e). They allow a variety of analysis possibilities:
Computation of a large variety of FBAT-statistics and their power for nuclear families and for extended pedigrees. - Multivariate FBATs for multiple phenotypes: FBAT-GEE and FBAT-PC. FBAT-GEE is based on the generalized estimating equation approach (Lange et al 2003). FBAT-PC is based on principal components that maximize the heritability (in preparation).
- FBATs for time to onset data/survival data (logrank-FBAT and Wilcoxon-FBAT, FBAT-EXP).
- Permutation tests for certain FBAT statistics.
- Transformation tools for continuous phenotypes that are not normally distributed.
- Conditional power calculations for all implemented FBATs.
- Construction of the most powerful FBAT-statistic.
- Including predictor variables in the FBAT.
- Including gene-environment/drug interactions in the FBAT statistic.
- Various estimation routines to estimate the genetic effect size.
- Screening methods to select the most "promising" combinations of markers and phenotypes without biasing the significance level of the FBAT statistic computed subsequently.
PBAT Copy Number Analysis
PBAT now supports the testing for copy-number variation (CNV) in a family-based setting as discussed in [Ionita-Laza 2008]. In conjunction with the copy number analysis module (CNAM), you can quickly:
- Normalize copy number intensity data
- Correct for batch effects using Eigenstrat-based PCA
- Filter out "poor quality" markers
- Join log2 ratios with pedigree/phenotype information
- Perform whole genome association tests
All robustness properties of the FBAT approach are maintained as in PBAT for SNP analysis. In addition, all previously-developed FBAT extensions, including FBATs for time-to-onset, multivariate FBATs, and FBAT-testing strategies, can be directly transferred to the analysis of CNVs.
Graphical User Interface
Golden Helix PBAT’s graphical user interface provides spreadsheets, drop down menus, and tabular parameter windows that streamlines analyses and helps you limit mistakes when inputting parameters. Results are presented in a spreadsheet that allows you to sort by various output variables.
Streamlined Data Import
Most programs cannot handle the growing size of today’s whole genome data sets. Golden Helix PBAT solves this by allowing you to easily import your pedigree, genotype and phenotype data separately and then joining them once they are in the program. Furthermore, you can rapidly import Affymetrix CHP files and files exported from Illumina’s BeadStudio Data Analysis Software.
Project Navigation
In accordance with sound laboratory practices, a project navigator automatically time-stamps and logs each analysis step and provides efficient means for tracking and annotating results. You can also share project files, which is particularly helpful when collaborating on projects.
Sparse Data Storage Technology
Efficiently handle large-scale data sets. Golden Helix PBAT offers sparse data storage technology that enables you to import, store, and export your data into exceptionally compact data storage files - DSF and GHD. These files utilize a fraction of the disk space and RAM as ordinary text files. With sparse storage you can rapidly import large-scale whole-genome data sets, analyze them with conventional hardware, and efficiently share them among colleagues and collaborators. Your entire WGA study can fit on a simple USB Flash drive.
Grid Computing and Parallel Processing Support
PBAT analysis with whole genome scans and/or extended pedigrees is computationally intensive and may take days or even weeks to run with a single processor. Get your research done faster by configuring PBAT to take advantage of multi-core and multi-processor systems or in a distributed grid environment using Condor® or the United Devices’ Grid MP™ platform. Using a grid enables the submitting of large, complex jobs in parallel to a wide variety of computing platforms, which maximizes distribution and throughput while making better use of otherwise idle cycles on existing hardware. Ultimately this can cut PBAT run times from weeks to a matter of hours or even minutes.
Exclusive Upgrades
Ensure you’re ahead of the curve. Enhancements to Golden Helix PBAT are developed jointly by Christoph Lange and Golden Helix and contain exclusive upgrades and bug fixes not supported in command-line PBAT.
References
Iuliana Ionita-Laza, George H. Perry, Benjamin A. Raby, Barbara Klanderman, Charles Lee,
Nan M. Laird, Scott T. Weiss, Christoph Lange
Published Online: Jan 28 2008 1:55PM
DOI: 10.1002/gepi.2030
