Description of bioinformatics tools and methods offered by BioData Ltd.

We have created several methods and software packages that facilitate the following genotyping tasks:

1) SNP selection
2) PCR primer design around SNPs
3) prediction and modeling of interactions on genotyping microarray
4) genotype and haplotype analysis, htSNP selection

1. SNP and candidate gene selection 

Our SNP selection software PickSNP allows flexible selection of genomic region for SNP selection.

Any region from the human genome can be defined by:

- physical location,
- chromosome band or
- gene IDs from the ENSEMBL database.

Any number of gene regions can be studied. Candidate genes can be selected automatically according to various criteria:

- all genes with given InterPro domain
- all genes with given PFAM domain
- all genes with given OMIM identifier
- all genes with given Gene Ontology identifier

SNP-gene relations are taken into account. The following criteria can be applied to SNP selection:

- exonic SNPs
- genic SNPs (exons + introns)
- promoter SNPs (region in front of 1^st exon)
- all SNPs with certain density (uniform distribution over the region) 
- all SNPs from this region

Flanking region of any size can be added to exonic, genic or promoter SNPs.

Different quality criteria for SNP selection can be used:

- APEX primer quality for given SNP (dimer formation or presence of direct repeats)
- presence of the SNP in the SNP consortium and/or HGVBASE databases
- allele frequencies in dbSNP (mostly unknown)

2. High quality PCR primers for all selected SNPs

Automated PCR primer design around selected SNPs. 
Automated PCR multiplex. The multiplx program tests following compatibility criteria and combines compatible PCR primers into groups:

          - primer-primer interactions
          - primer dimer formation
          - primer-product interactions
          - genome test for all possible PCR primer pairs
          - length differences between PCR products

These PCR primer design programs can handle datasets with more than 100 000 SNPs

3. ChipTester

A program for chip-based genotyping that models interactions on the genotyping microarray. Tests for potential interactions between APEX primers and PCR products on the chip. SNPs that might generate false signals are removed or replaced at this step.

4. Genotype and haplotype data analysis at large scale

- Haplotype inference from population data or family data.
- Haplotype block detection and htSNP selection with dynamic programming algorithm.
- Exon-based or gene-based htSNP selection if haplotype structure is known. We can overlay the haplotype map with genomic information to facilitate haplotype block and htSNP selection for large-scale projects. We have done simulations that indicate that all exons in the human genome can be genotyped with approximately 60 000 htSNPs.
- New method for htSNP selection for large, population-based genotyping projects. In population-based genotyping projects the haplotype inference is done with computational methods and therefore contains errors. We have created a new htSNP selection method that does not require computational inference of haplotypes and guarantees correct haplotype detection of each genotyped individual (manuscript submitted).

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