SARS: A Multidisciplinary SARS: A Multidisciplinary Exploration Exploration

Nitya JacobNitya JacobDoug GrahamDoug GrahamEloise CarterEloise Carter

Manish ChakrabartiManish Chakrabarti

Teaching with an EpidemicTeaching with an Epidemic

SARS as a topic to introduce problem SARS as a topic to introduce problem solving in biology, medical epidemiology solving in biology, medical epidemiology and bioinformaticsand bioinformatics

Diverse sources of information on SARS Diverse sources of information on SARS used to introduce the topicused to introduce the topic

Platform for developing questions that Platform for developing questions that engage students engage students

Use of existing data/information to develop Use of existing data/information to develop analysis skills for future projectsanalysis skills for future projects

SARS – Severe Acute Respiratory SARS – Severe Acute Respiratory SyndromeSyndrome

Coronovirus – SARS Coronovirus – SARS CoVCoV

Global epidemic 2003Global epidemic 2003 8,000 cases, 24 8,000 cases, 24

countriescountries Spread by respiratory Spread by respiratory

dropletsdroplets

SARS - SymptomsSARS - Symptoms

High fever > 100oCHigh fever > 100oC HeadachesHeadaches Body aches and painsBody aches and pains All pneumoniaAll pneumonia

SARS – Integrating TopicsSARS – Integrating Topics

BiogeographyBiogeography Epidemiology/BiologyEpidemiology/Biology Detection and DiagnosisDetection and Diagnosis Time LineTime Line GenomeGenome PhylogenyPhylogeny Bioinformatic ToolsBioinformatic Tools Public Health – Quarantine, Education, etc.Public Health – Quarantine, Education, etc. Vaccine DevelopmentVaccine Development

Questions to ExploreQuestions to Explore

Evolution/variation of sequences encoding Evolution/variation of sequences encoding specific proteins (Orf 1ab vs. spike)specific proteins (Orf 1ab vs. spike)

Differences between CoronavirusesDifferences between Coronaviruses Differences between strains from China Differences between strains from China

and Taiwan vs. strains transmitted to and Taiwan vs. strains transmitted to North AmericaNorth America

SARS Sequences AvailableSARS Sequences Available

FULL GENOME SEQUENCESFULL GENOME SEQUENCES

TOR2TOR2 SIN2500, SIN2748, SIN2774, SIN2677, SIN2679SIN2500, SIN2748, SIN2774, SIN2677, SIN2679 URBANIURBANI HKU39849HKU39849 BJO1BJO1 HKU39849HKU39849 CUHKUW1, CUHK-Su10CUHKUW1, CUHK-Su10 LLJ-2004LLJ-2004 HSR1 – ItalyHSR1 – Italy Frankfurt 1Frankfurt 1 Sino1-11Sino1-11 GD01GD01

www.ncbi.nlm.nih.govSalemi et al, 2004

SARS Protein SequencesSARS Protein Sequences

Spike glycoprotein (S)Spike glycoprotein (S) Replicase polyprotein (Orf1ab)Replicase polyprotein (Orf1ab) Nucleocapsid (N)Nucleocapsid (N) Membrane protein (M)Membrane protein (M)

www.ncbi.nlm.nih.gov

EpidemiologyEpidemiology

Origin of SARS coronavirus?Origin of SARS coronavirus? Case definitionCase definition Factors (biological/cultural) contributing to Factors (biological/cultural) contributing to

global spreadglobal spread

BioinformaticsBioinformatics

Target Audience: Computer Science, Math and Target Audience: Computer Science, Math and Statistics students.Statistics students.Exploration Ideas:Exploration Ideas: Search NCBI for the complete SARS Co-v genome Search NCBI for the complete SARS Co-v genome

(Accession number: NC_004718)(Accession number: NC_004718) Download the entire sequence in FASTA format (goal: Download the entire sequence in FASTA format (goal:

learn about FASTA)learn about FASTA) Now download the sequence in XML format (learn Now download the sequence in XML format (learn

about the different XML formats such as GBSeqXML, about the different XML formats such as GBSeqXML, TinySeqXM, etc.)TinySeqXM, etc.)

Play with the NCBI Protein Viewer (Cn3D) to explore Play with the NCBI Protein Viewer (Cn3D) to explore the structure of Nsp9 Protein From Sars-Coronavirus.the structure of Nsp9 Protein From Sars-Coronavirus.

SARS ResourcesSARS Resources

Epidemic! The Natural History of Disease at the San Epidemic! The Natural History of Disease at the San Diego Natural History Museum Diego Natural History Museum www.sdnhm.org/exhibits/epidemic/resources.htmlwww.sdnhm.org/exhibits/epidemic/resources.html

Useful site for additional web links and info Useful site for additional web links and info http://microvet.arizona.edu/Courses/MIC438/collectjc04.http://microvet.arizona.edu/Courses/MIC438/collectjc04.html (images above)html (images above)

CDC information CDC information http://www.cdc.gov/ncidod/EID/vol5no2/snacken.htmhttp://www.cdc.gov/ncidod/EID/vol5no2/snacken.htm

Maps and photos Maps and photos http://www.geo.arizona.edu/Antevs/nats104/00lect24sarshttp://www.geo.arizona.edu/Antevs/nats104/00lect24sars.html (images above).html (images above)

Resources for Evolution and Resources for Evolution and PhylogenyPhylogeny

Salemi et al. 2004. “Severe Acute Respiratory Syndrome Salemi et al. 2004. “Severe Acute Respiratory Syndrome Coronavirus sequence characteristics and evolutionary Coronavirus sequence characteristics and evolutionary rate estimate from maximum likelihood analysis”. rate estimate from maximum likelihood analysis”. J of J of VirologyVirology 78:1602-1603. 78:1602-1603.

Chinese SARS Molecular Epidemiology Consortium. Chinese SARS Molecular Epidemiology Consortium. 2004. “Molecular evolution of the SARS coronavirus 2004. “Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China.” during the course of the SARS epidemic in China.” ScienceScience 303:1666-1669. 303:1666-1669.

Lan et al. 2005. “Phylogenetic analysis and sequence Lan et al. 2005. “Phylogenetic analysis and sequence comparison of structural and non-structural SARS comparison of structural and non-structural SARS coronavirus proteins in Taiwan.” coronavirus proteins in Taiwan.” Infect. Genet. EvolInfect. Genet. Evol. . 5:261-95:261-9

Resources for BioinformaticsResources for Bioinformatics

Complete SARS GenomeComplete SARS Genome Unique and conserved features of genome Unique and conserved features of genome

and proteome of SARS-coronavirus, an and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 early split-off from the coronavirus group 2 lineage - Snijder,E.J at al, J. Mol. Biol. 331 lineage - Snijder,E.J at al, J. Mol. Biol. 331 (5), 991-1004 (2003) PUBMED 12927536 (5), 991-1004 (2003) PUBMED 12927536

ConclusionsConclusions

This approach could be used in other This approach could be used in other areas of studyareas of study

Epidemic diseases capture interest and Epidemic diseases capture interest and integrate diverse skills and conceptsintegrate diverse skills and concepts

Meaningful connection of bioinformatics to Meaningful connection of bioinformatics to timely and engaging problemstimely and engaging problems

Find your favorite disease!Find your favorite disease!