An analysis of “Bioinformatics analysis of SARS coronavirus genome polymorphism” by Pavlović-Lažetić, et. al

Angela BrooksJuly 9, 2004SoCalBSI Article Presentation

Outline

Background Purpose Experimental Methods Results Conclusions Possible Future Studies Importance of the work to society

Background The authors analyzed the genomes of 38

isolates of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) Isolates: virus “strains” that are apart/cut off

from one another by location Looking for:

single nucleotide polymorphisms(SNPs) insertions and deletions sequence similaritybetween isolates to determine the phylogeny of the

SARS-CoV isolates

SNPs – Single Nucleotide Polymorphisms A single point mutation

in the genome Types of mutations

caused by SNPs: Silent

no change Missense

AA change in protein product

Nonsense Change AA to “stop”

Other Change in other

functional/regulatory region

Purpose of Paper

Establish the origin of the virus. Find regions in genome with high

levels of sequence polymorphisms Discover the evolutionary path of the

virus lead towards preventing or curing the

disease that it causes

2 Step Sequence Comparisons

1. Structurally Identical Parts

Identify regions of insertions and deletions with a reference set

2. SNPs in Structurally Identical Parts

From regions in Part 1, find SNPs in those regions

2 Step Sequence Comparisons

1. Structurally Identical Parts Similar to sequence

alignment

2. SNPs in Structurally Identical Parts

Reference Set (database)

Other isolate sequences (queries)

How were sequences obtained?

Our old friend NCBI:Label ID Accession No. Length Revision date Country/Source

1. TWH Ap006557.1 29727 02-AUG-2003 Taiwan: patient #01

TWC2 Ay362698.1 13-AUG-2003 Taiwan: Hoping Hospital

2. TWC3 Ay362699.1 29727 13-AUG-2003 Taiwan: Hoping Hospital

3. TWK Ap006559.1 29727 02-AUG-2003 Taiwan: patient #06

4. TWS Ap006560.1 29727 02-AUG-2003 Taiwan: patient #04

5. TWY Ap006561.1 29727 02-AUG-2003 Taiwan: patient #02

6. Urbani Ay278741.1 29727 12-AUG-2003 USA: Atlanta

7. TWJ Ap006558.1 29725 02-AUG-2003 Taiwan: patient #043

8. TWC Ay321118.1 29725 26-JUN-2003 Taiwan, first fatal case

Finding structural similarity

SNPs identified

Density distribution of polymorphisms

Qualitative Analysis of Sequence Variation

Based on structural similarity and SNPs, a tree was constructed to show sequence divergence

ClustalW used as a control for tree

ClustalW with PhyloDraw was used to draw a tree for comparison with “homemade” tree ZMY1 and ZJ01 are

distant from representative group.

Side by Side Comparison of Trees

New Problems to Address Not much analysis was done on results from

study i.e. Found SNPs and structurally similar regions but

not significant without analysis What could be analyzed further?

Examine regions of conservation for functional importance

Examine phenotypic affect of amino acid mutation For isolates in a similar group, compare phenotypic

characteristics to genotypic similarites Uncover phenotypic/genotypic

relationships

Why is SARS-CoV research important?

Previous year’s “outbreak” uncovered in China Anxiety over viruses Possible bioterrorism Understanding SARS-CoV may help to

understand similar virus