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MPDA: microarray pooled DNA analyzer.

Yang HC, Huang MC, Li LH, Lin CH, Yu AL, Diccianni MB, Wu JY, Chen YT, Fann CS - BMC Bioinformatics (2008)

Bottom Line: This new technique uses pooled DNA, thereby reducing costs associated with the typing of DNA from numerous individuals.Thus, the technique provides an overall cost-effective solution for large-scale genomic/genetic research.The third analysis indicates that MPDA is cost-effective and reliable for association mapping.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. hsinchou@stat.sinica.edu.tw

ABSTRACT

Background: Microarray-based pooled DNA experiments that combine the merits of DNA pooling and gene chip technology constitute a pivotal advance in biotechnology. This new technique uses pooled DNA, thereby reducing costs associated with the typing of DNA from numerous individuals. Moreover, use of an oligonucleotide gene chip reduces costs related to processing various DNA segments (e.g., primers, reagents). Thus, the technique provides an overall cost-effective solution for large-scale genomic/genetic research. However, few publicly shared tools are available to systematically analyze the rapidly accumulating volume of whole-genome pooled DNA data.

Results: We propose a generalized concept of pooled DNA and present a user-friendly tool named Microarray Pooled DNA Analyzer (MPDA) that we developed to analyze hybridization intensity data from microarray-based pooled DNA experiments. MPDA enables whole-genome DNA preferential amplification/hybridization analysis, allele frequency estimation, association mapping, allelic imbalance detection, and permits integration with shared data resources online. Graphic and numerical outputs from MPDA support global and detailed inspection of large amounts of genomic data. Four whole-genome data analyses are used to illustrate the major functionalities of MPDA. The first analysis shows that MPDA can characterize genomic patterns of preferential amplification/hybridization and provide calibration information for pooled DNA data analysis. The second analysis demonstrates that MPDA can accurately estimate allele frequencies. The third analysis indicates that MPDA is cost-effective and reliable for association mapping. The final analysis shows that MPDA can identify regions of chromosomal aberration in cancer without paired-normal tissue.

Conclusion: MPDA, the software that integrates pooled DNA association analysis and allelic imbalance analysis, provides a convenient analysis system for extensive whole-genome pooled DNA data analysis. The software, user manual and illustrated examples are freely available online at the MPDA website listed in the Availability and requirements section.

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Related in: MedlinePlus

Genome-wide single- and multi-locus allelic imbalance analyses – Amplification of both ends of a chromosome but copy-neutral LOH in the middle part of the same chromosome.
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Figure 8: Genome-wide single- and multi-locus allelic imbalance analyses – Amplification of both ends of a chromosome but copy-neutral LOH in the middle part of the same chromosome.

Mentions: Figure 6 – Figure 10 show representative examples of several abnormal patterns identified by this analysis; these correspond to trisomy (Figure 6), deletion of a microscopic chromosomal segment (Figure 7), amplification of both ends of a chromosome and copy-neutral LOH in the middle of the same chromosome (Figure 8), deletion of a submicroscopic chromosomal region (Figure 9), and common deletion of the TCRα/δ locus in three ALL patients (Figure 10). In each figure, the horizontal axis denotes the physical position of SNPs (scale in megabases, Mb), the left vertical axis denotes AF, and the right vertical axis denotes the score value. Each point stands for one SNP. Non-allelic imbalance SNPs (NAI SNPs) are represented by blue points, and allelic imbalance SNPs (AI SNPs), identified by the single-locus allelic imbalance analysis, are represented by red points. The orange curve denotes the multilocus allelic imbalance cumulative sum statistic SCORE1, and the purple curve denotes the LOH cumulative sum statistic SCORE2. Results on specific chromosomes are used to illustrate different types of AI situations and the corresponding chromosomal aberrations, where dashed green lines define boundaries of aberrant regions identified by MPDA.


MPDA: microarray pooled DNA analyzer.

Yang HC, Huang MC, Li LH, Lin CH, Yu AL, Diccianni MB, Wu JY, Chen YT, Fann CS - BMC Bioinformatics (2008)

Genome-wide single- and multi-locus allelic imbalance analyses – Amplification of both ends of a chromosome but copy-neutral LOH in the middle part of the same chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2387178&req=5

Figure 8: Genome-wide single- and multi-locus allelic imbalance analyses – Amplification of both ends of a chromosome but copy-neutral LOH in the middle part of the same chromosome.
Mentions: Figure 6 – Figure 10 show representative examples of several abnormal patterns identified by this analysis; these correspond to trisomy (Figure 6), deletion of a microscopic chromosomal segment (Figure 7), amplification of both ends of a chromosome and copy-neutral LOH in the middle of the same chromosome (Figure 8), deletion of a submicroscopic chromosomal region (Figure 9), and common deletion of the TCRα/δ locus in three ALL patients (Figure 10). In each figure, the horizontal axis denotes the physical position of SNPs (scale in megabases, Mb), the left vertical axis denotes AF, and the right vertical axis denotes the score value. Each point stands for one SNP. Non-allelic imbalance SNPs (NAI SNPs) are represented by blue points, and allelic imbalance SNPs (AI SNPs), identified by the single-locus allelic imbalance analysis, are represented by red points. The orange curve denotes the multilocus allelic imbalance cumulative sum statistic SCORE1, and the purple curve denotes the LOH cumulative sum statistic SCORE2. Results on specific chromosomes are used to illustrate different types of AI situations and the corresponding chromosomal aberrations, where dashed green lines define boundaries of aberrant regions identified by MPDA.

Bottom Line: This new technique uses pooled DNA, thereby reducing costs associated with the typing of DNA from numerous individuals.Thus, the technique provides an overall cost-effective solution for large-scale genomic/genetic research.The third analysis indicates that MPDA is cost-effective and reliable for association mapping.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. hsinchou@stat.sinica.edu.tw

ABSTRACT

Background: Microarray-based pooled DNA experiments that combine the merits of DNA pooling and gene chip technology constitute a pivotal advance in biotechnology. This new technique uses pooled DNA, thereby reducing costs associated with the typing of DNA from numerous individuals. Moreover, use of an oligonucleotide gene chip reduces costs related to processing various DNA segments (e.g., primers, reagents). Thus, the technique provides an overall cost-effective solution for large-scale genomic/genetic research. However, few publicly shared tools are available to systematically analyze the rapidly accumulating volume of whole-genome pooled DNA data.

Results: We propose a generalized concept of pooled DNA and present a user-friendly tool named Microarray Pooled DNA Analyzer (MPDA) that we developed to analyze hybridization intensity data from microarray-based pooled DNA experiments. MPDA enables whole-genome DNA preferential amplification/hybridization analysis, allele frequency estimation, association mapping, allelic imbalance detection, and permits integration with shared data resources online. Graphic and numerical outputs from MPDA support global and detailed inspection of large amounts of genomic data. Four whole-genome data analyses are used to illustrate the major functionalities of MPDA. The first analysis shows that MPDA can characterize genomic patterns of preferential amplification/hybridization and provide calibration information for pooled DNA data analysis. The second analysis demonstrates that MPDA can accurately estimate allele frequencies. The third analysis indicates that MPDA is cost-effective and reliable for association mapping. The final analysis shows that MPDA can identify regions of chromosomal aberration in cancer without paired-normal tissue.

Conclusion: MPDA, the software that integrates pooled DNA association analysis and allelic imbalance analysis, provides a convenient analysis system for extensive whole-genome pooled DNA data analysis. The software, user manual and illustrated examples are freely available online at the MPDA website listed in the Availability and requirements section.

Show MeSH
Related in: MedlinePlus