phenotype information for existing gwas studies
DESCRIPTION
2013 Summit on Clinical Research InformaticsTRANSCRIPT
Phenotype Information Retrieval for Existing GWAS
Studies
Neda Alipanah, Ph.D. University of California San Diego
March 2013
Motivation • The database of Genotypes and Phenotypes (dbGaP) is
archiving the results of different Genome Wide Association Studies (GWAS).
• Phenotype variables are not harmonized across studies.
• Redundant phenotype identifiers for the same phenotype.
• dbGaP lacks semantic relations among its variables.
• Search on phenotypes is not accurate.
Goals • Standardize dbGaP information to allow accurate,
reusable and
• Quick retrieval of information
Problem Statement (Example of Redundant Variables) dbGaP Structure
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000007.v18.p7
dbGaP Study phs000007.v18.p7
id=” phv00003636.v1 ”, Description=” HEART:
HYPERTENSIVE HEART DISEASE ”, name=” FK414”,
version=“1”, Logical Max=”--”, Logical Minimum=”--”, unit=”--”, type=”string”
id=” phv00008678.v3 ”, Description=” CDI: HYPERTENSIVE
HEART DISEASE ”, name=” C334 ”,
version=“3”, Logical Max=”--”, Logical Minimum=”--”, unit=”--”,
type=”text”
N Alipanah, H Kim, L Ohno-Machado: Building an Ontology of Phenotypes for Existing GWAS Studies. Healthcare Informatics, Imaging and Systems Biology (HISB), 2012 IEEE Second International Conference on , vol., no., pp.111, 27-28 Sept. 2012
Problem Statement (Example of Semantic Relation) dbGaP Structure
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.p1
dbGaP Study phs000284.v1.p1
id=” phv00123020.v1”, Description=” CVD: self report of MD
dx of cvd ”, name=” cvd”,
version=“1”, value=“Yes, No, Not assessed”
Id=” phv00123021.v1 ”, Description=” CVD: self report of MD
dx of cvd (missing recoded as no) ”, name=”cvdx”,
version=“1”, value=“Yes, No, Not assessed”
Proposed Solution
� Build an information model ◦ Indexing the phenotype variables
semantically ◦ No Redundancy
Example:
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
Heart Disease
Cardiovascular Disease
Id=“phv00124261.v1 ”
id=” phv00008678.v3” phv00123021.v1 phv00123020.v1
…….
Methods
I. String-based Variables Distance Calculation
II. Semantic Hierarchy Extraction on Revised
Clusters
III. Classification and Ontology Creation
IV. sdGaP Information Retrieval
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
1. String-based Variables Distance Calculation
1- Property Extraction Name, Description, Type, Unit, …,and (Max-Min) values 2- UMLS Expansion
Expand Variable Description with MetaMap
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
1. String-based Variables Distance Calculation 3- Distance Computation Description: Vector Space Model Matching Name Similarity: Jaro-Winkler String Matcher Type: Exact String Match Unit: Exact String Match (Max-Min) values: Subset Matching 4- Build Distance Matrix Compute the Distance between every pair of Variables.
5- Cluster based on Distance Matrix Variables with the same distance to other variables are clustered together.
II. Semantic Hierarchy Extraction on Revised Clusters 1. Build String-based distance matrix for variables in a single assigned
cluster.
2. Sub-cluster variables and calculate semantically relevant (similar) variables.
3. Assign labels to sub-clusters based on the relevant UMLS Concept Unique Identifier.
4. Perform re-clustering to find smaller group of relevant variables.
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
id=”phv00122015”, Description=”Age at time of Study”,
name=”age”, version=“1”, Logical Max=”65”, Logical
Minimum=”18”, unit=”Years”, type=”decimal”
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
dbGaP Study phs000284.v1.pht001903.v1.CFS_CARe_ECG.data_dict_2011_02_07
III. Classification and (sdGaP) Ontology Creation 1. Start with UMLS semantic network. 2. Extract corresponding sub class (PAR/CHD) hierarchy using the
UMLS hierarchy table (MRREL table).
3. Instantiate the phenotype variables to the UMLS CUIs. (Not for higher levels)
4. Populate the related constraints in sdGaP
IV. sdGaP Information Retrieval 1. Use sdGaP Ontology structure to expand the query � Density Measure (DM)
Density(A)=3 Density(B)=0 Density(D)=0
Density(A)=2 Density(D)=1 Density(B)=1 Density(E)=1 Density(C)=0
IV. Result � Dataset: Cleveland Family Study (CFS) with 5 data sets and 2,339
phenotype variables. (phs000284.v1.p1) � Use Weka Tool for Xmean clustering. � The X-mean clustering resulted in 35 clusters for relevant variables. � Reorganized into 23 clusters by domain expert reviewers
IV. Result of Concept-based Retrieval (Improvement of Subclass Expansion)
� Query =“Cardiovascular Disease”
Query Expansion={Heart } in “Disease Cluster” Recall Improvement 2/45=0.04 to 18/45=0.4
Cardiovascular Disease
Heart Disease
phv00123021.v1
Phv00122274.v1
Phv00122277.v1
phv00123020.v1
Phv00122280.v1
Phv00122281.v1
Phv00122283.v1
Phv00122284.v1
Phv00122285.v1
Phv00122286.v1
……
Conclusion
� Extracting Standard Reusable Information Model From UMLS
� Improving Information Retrieval by
Organizing Phenotype Variables and Instantiate them to Data Model
Limitation � Clustering based on Distance Calculation
is Semi-automated Computation. � Instantiating variables to lower levels of
hierarchy needs domain expert review. � Only instances of lower level of
hierarchies are considered in ontology building.
� For large data, distance calculation and clustering needs more advance algorithms.
Acknowledgement
� Supported by Grants ◦ UH2HL108785 (NHLBI) ◦ R01HS019913 (AHRQ)
� Supervision of Dr. Lucila Ohno-Machado.