1. Identifying deleterious Single Nucleotide Polymorphisms using multiple sequence alignments CMSC858P Project by Maya Zuhl

2. What is SNP? SNPs - Single nucleotide polymorphisms (SNPs [i] ) account for the majority of genetic variation in the human population. The majority of monogenic (single gene) diseases are mediated by single base changes. (snps3d)‏ ‏

3. Why it is important to study SNPs? Various combination of SNPs make us susceptible to wide- spread diseases like Alzheimer, heart diseases, diabetes, etc. At present, the relevant information is still very incomplete and scattered across many databases and thousands of articles.

4. How do we know that a SNP causes a disease? There are various method to predict whether a SNP is deleterious or not For example, profile method - looking for SNPs that appear in protein/gene region that does not change much through evolution (highly conserved)‏

5. What do I propose? Get a set of genes for research – genes related to Asthma disease (to narrow down the number of researched sequences)‏ Retrieve SNPs appearing in these genes using automatic literature mining software Perform PSI-BLAST for each sequence and calculate position- specific score matrix (PSSM)‏ Using PSSM scores to predict which of the SNPs is deleterious.

6. Set of genes Set of SNPs Candidate genes snps3d.org PSI-BLAST for each gene sequence Set of genes PSSM Matrix Set of deleterious SNPs for each gene NCBI bio-medical articles' abstracts

7. Benchmarking? Human annotated SNPs database - Human Gene Mutation Database (HGMD)‏ Question: Why do we need my project if there exists database like HGMD? Answer: Databases like HGMD are compiled by exhaustive reading of hundreds of articles. While my project offers a way to compile such database much quicker and easier. It is not a perfect solution, but a good start.

8. Questions?