HL7 Clinical Genomics SIG Jan 22, 2004

1. HL7 Clinical Genomics SIG Jan 22, 2004 Usha Reddy, PhD IBM Life Sciences

2. Standards in Biology Various XML formats - GAME - BIOML - BSML - AGAVE - GBSeqXML - XEMBL

3. Genotype • HapMap XML http://hapmap.cshl.org/xml-schema/2003-10-14/hapmap.xsd • PharmGKB http://pharmgkb.org/schema/index.html Its aim is to aid researchers in understanding how genetic variation among individuals contributes to differences in reactions to drugs.

4. HAPMAP • HapMap project is an international effort to determine • common patterns of DNA sequence variation in the • human genome. • HapMap allows discovery of sequence variants that • affect common disease. • Helps in choosing targets for therapeutic intervention • Project data is freely available at the HapMap Data • Coordination Center (DCC) • The HapMap Data Coordination Center (DCC) coordinates • and manages project data flow, data storage, data release • and presentation to the community.

5. The HapMap schema consists of several small files that each describes a single kind of large-ish object (a SNP, a protocol), several related smaller ones or common datatypes or element groups. The main artifacts of HapMap XML schema are: snp - the unique SNP clusters mapping to the human genome assembly. The XML is based largely on the dbSNP reference SNP records. It includes the following attributes: lsid – snp_class – sequence - 5' and 3' sequences flanking the variation and the variation itself. genomic_locations neighbor_snps genotype - contains the genotype element, which represents a single genotype for a sample. assay - contains the assay element, which represents an assay for a single SNP batch_submission - a container for batch submission data of various kinds. In other words it wraps together other HapMap XML elements. protocol - captures information about e.g. the procedure of designing an assay sample - enables storing of detailed information on the HapMap samples collection. individual - used for describing an individual whose sample will be used in the HapMap project.

6. HapMap XML <xs:include schemaLocation="snp.xsd" /> <xs:include schemaLocation="batch_submission.xsd" /> <xs:include schemaLocation="batch_allocation.xsd" /> <xs:include schemaLocation="assay_submission.xsd" /> <xs:include schemaLocation="genotype_submission.xsd" /> <xs:include schemaLocation="genotype_set.xsd" /> <xs:include schemaLocation="labgroup.xsd" /> <xs:include schemaLocation="protocol.xsd" /> <xs:include schemaLocation="assay.xsd" /> <xs:include schemaLocation="individual.xsd" /> <xs:include schemaLocation="haplotype.xsd" /> <xs:include schemaLocation="sample.xsd" /> <xs:include schemaLocation="simple_types.xsd" /> <xs:include schemaLocation="complex_types.xsd" /> <xs:include schemaLocation="allele_frequency.xsd" /> </xs:schema> http://hapmap.cshl.org/xml-schema/2003-10-14/hapmap.xsd

7. PharmaGKB Genomic data, molecular and cellular phenotype data, and clinical phenotype data are accepted from the scientific community at large. These data are then organized and the relationships between genes and drugs are then categorized into the following categories: CO Clinical Outcome Genetic variations in the response to drugs can cause measurable differences in clinical endpoints such as rates of cure, morbidity, side effects, and death. Data in this category demonstrate that genetic variability in the context of a drug effect significantly changes medical outcomes. PD Pharmacodynamics and Drug Response Genetic variation in drug targets can cause measurable differences in the response of an organism to a drug. PK Pharmacokinetics Genetic variation in processes involved in the absorption, distribution, metabolism, or elimination of a drug can result in changes in drug availability. FA Molecular and Cellular Functional Assays Genetic variation can alter results of molecular and cellular functional assays, and this may correlate with variations in the organism's drug response. GN Genotype Genotype is the internally coded, heritable information carried by the organism

8. PharmGKB • Schema Definition The PharmGKB XML schema definition is available here: root.xsd: The root of the PharmGKB schema. It pulls in the other schema files below. types.xsd: Defines common XML elements used throughout the PharmGKB schema. types-sequence.xsd: Defines common XML elements for sequences used throughout the PharmGKB schema. sequence.xsd: Defines sequence related XML elements. experiment.xsd: Defines experiment related XML elements. haplotype.xsd: Defines haplotype related XML elements. sampleset.xsd: Defines sample set and subject related XML elements. drug.xsd: Defines drug related XML elements. disease.xsd: Defines disease related XML elements. http://pharmgkb.org/schema/index.html