Embed Size (px)
Citation preview
LIPID MAPS
LIPID MAPS: Bioinformatics Organizational Structure
• Shankar Subramaniam (PI)• Eoin Fahy (Coordinator) – Lipid Chemistry, MS data analysis
• M Madhusudan – LIMS
• Dawn Cotter – LIPID MAPS Website
• Babu Guda – Lipid Biology (Genes, proteins, pathways)
• Purnima Guda – Lipid Biology (Genes, proteins, pathways)
LIPID MAPS: Hardware/Software Infrastructure
• Utilization of existing server infrastructure at SDSC• Primarily Sun Solaris-based
• Additional LIPID MAPS Solaris server for chemistry development work
• Extension of existing Oracle databases used by the AFCS project to cater for LIPID MAPS needs
• Data backup/recovery/security already in place for Oracle DB servers and other bioinformatics servers
LIPID MAPS: User Software Infrastructure
• Web –based front-end• Familiar web browser interface• Easy learning curve• Online help
• Access control for public vs private areas of website
• CVS versioning control
LIPID MAPS: Data Collection
• Experimental conditions/protocols• LIMS system • Java based – client software runs on multiple platforms
(e.g. Windows)• Use of barcodes for reagents,solutions,protocols• Interfaces with Oracle database at SDSC• Multi-level access control
LIPID MAPS LIMS System
Benefits:1) Data validation2) Maintain Data Integrity3) Standardize Data Inputs/Outputs4) Automate Data Transfer between Labs5) Paper Free Electronic Notebook
LIPID MAPS Laboratory Information Management System (LIMS)
Sample Preparation
Sample Processing
Sample Handling
Data Input GUIs
OracleDatabase
Barcode
Test tube/Sample vial
IP Barcode printer
Barcode Scanner
Sample tracking
Data Integrity/ Storage
LIPID MAPS LIMS: Solution GUI
LIPID MAPS: Data Collection/Organization
• Existing Lipid structural data: • LIPIDAT Database: 12,528 structures• LipidBank Database: 6,565 structures• Currently merged and stored in Oracle database• Oracle chemistry cartridge (Sun Server)
– Import molfile and Chemdraw formats using Oracle procedures– Structures are stored within Oracle tables– Exact or substructure search over the web
• Add novel lipid structures as they become available• Objective: Database of unique lipid structures
LIPID MAPS: Key Chemistry Table Fields
• Lipid_ID (number)
• Compound (Blob)
• Core Class
• Main Class
• Sub Class
• Lipidat_ID
• Lipidbank_ID
• Common Name
• Synonyms
• Systematic name
• Molecular weight
• Formula
LIPID MAPS: Data Integration from public sources• Key issues: • Author permissions (LipidBank)
• Importing structure file formats (molfile,Chemdraw,gifs)
• Ambiguities in structures (esp. stereochemistry)
• Consistency in drawing structures within a class
• Classification conventions
• Nomenclature conventions
• Adding updated records (Tracking LIPIDAT/LipidBank ID’s)
LIPID MAPS Structure Database-Approach
High quality structures/names(Core labs,Avanti, others)
(Empty)
New structures identified in LIPID MAPS experiments
LIPID MAPS DB
LIPIDAT
LIPIDBANK
Editing
Editing
LIPID MAPS Classification:Strategy
• 6 LIPID MAPS core classes– I: Fatty Acids /Eicosanoids [FA]– II: Neutral Lipids [NL]– III: Glycerophospholipids [GP]– IV: Sphingolipids [SP]– V: Sterols [ST]– VI: Isoprenoids [IP]
• Glycolipids [GL] represent an additional class outside these cores
• Additional sub-categories (Main class, Sub class) within cores.
LIPID MAPS: Core class-I: Fatty Acids and Conjugates
• I: Fatty Acids /Eicosanoids [FA]– Fatty Acids and Conjugates [1]
• Saturated Fatty Acids (a)• Unsaturated Fatty Acids (b)• Hydroxy and Keto Fatty Acids (c)• Fatty Acyl Amides (d)• Fatty Acyl CoAs (e)
– Eicosanoids [2]• Prostaglandins (a)• Leukotrienes (b)• Thromboxanes (c)• Lipoxins
– Oxidized Fatty Acids [3]
• Isoprostanes (a)• Neuroprostanes (b)
– Other [0]
LIPID MAPS: Core class - II: Neutral Lipids
• II: Neutral Lipids [NL]
– Monoacylglycerols [1]
– Diacylglycerols [2]
– Triacylglycerols [3]
– Sterol esters [4]
– Fatty Alcohols & Aldehydes [5]
– Wax esters [6]
– Other [0]
LIPID MAPS: Core class -III Glycerophospholipids
• III: Glycerophospholipids [GP]– Diacylglycerophospholipids [1]
• Diacylglycerophosphocholines (a)• Diacylglycerophosphoethanolamines (b)• Diacylglycerophosphoserines ©• Diacylglycerophosphoglycerols (d)• Diacylglycerophosphoglycerophosphates (e)• Diacylglycerophosphoinositols (f)• Diacylglycerophosphoinositolphosphates (g)• Diacylglycerophosphates (h)• Diacylglycerophosphoglycerophosphodiacylglycerols (I)• CDP-diacylglycerols
– Monoacylglycerophospholipids [2]
– Ether-linked glycerophospholipids [3]
– Oxidized Glycerophospholipids [4]
– Other [0]
LIPID MAPS: Core class -IV Sphingolipids
• IV: Sphingolipids [SP]– Sphingoid bases [1]
– Ceramides [2]
– Phosphosphingolipids [3]
– Neutral glycosphingolipids [4]
– Acidic glycosphingolipids [5]
– Other [0]
LIPID MAPS: Core class -V Sterols
• V: Sterols [ST]– Sterols [1]
– Steroids [2]
– Secosteroids [3]
– Steroid conjugates [4]
– Bile Acids and derivatives [5]
– Other [0]
LIPID MAPS: Core class -VI Isoprenoids• VI: Isoprenoids [IP]
– C5-C25 compounds [1]
– C30 compounds [2]
– Vitamins and Quinones [3]
– Dolichols [4]– Other [0]
LIPID MAPS: VII Glycolipids• Glycolipids [GL]
– Diacylglycerol glycans [1]
– Diacylglycerophosphoinositol glycans [2]
– Other [0]
LIPIDAT Phosphocholine structureStereochemical ambiguities, non-standard nomenclature
O
O
O
O
OPO
O-
O
N+
3,5,9-Trioxa-4-phosphatetracosan-1-aminium, 4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxotridecyl)oxy]-, inner salt, 4-oxide, (R)-
LIPID MAPS Phosphocholine structure
1,2-Didodecanoyl-sn-glycero-3-phosphocholine
(1,2-Dilauroyl-sn-glycero-3-phosphocholine)
O O
O
H O
O
P
O
O
-O
N+
LIPIDAT phosphoinositol structure Stereochemical ambiguities, non-standard nomenclature
D-myo-Inositol, 1-[2,3-bis[(1-oxotetradecyl)oxy]propyl hydrogen phosphate], (R)-
O O
O
O
O
O P
O
O
O
H
H
H
H
H
O
O
O
O
H
LIPID MAPS phosphoinositol structure
1,2-Ditetradecanoyl-sn-glycero-3-phospho -1D-myo-inositol
(1,2-Dimyristoyl-sn-glycero-3-phospho -1D-myo-inositol)
O O
O
H O
O
P
O
O-
O
HOOH
OHHO
HO
H
H
H
H
H
H
LIPID MAPS: Data Collection
• Experimental data: Mass spectrometry • ABI/SCIEX QTRAP 4000: file formats
• Experimental acquisition parameters
• Quantitation parameters
• Quantitation results
• CID spectra (fragmentation patterns)- JCAMP format
• LC elution profiles (image)
• Parsing programs have been written to interpret QTRAP 4000 data and export it to Oracle DB
LIPID MAPS :MS Data Query
LIPID MAPS :MS Data Query
LIPID MAPS :MS Data Query
Lipid MS database schema(Vanderbilt data)
LIPID
LIPID_IDHEAD_GROUP_ABBREVACYL_CARBONSACYL_DOUBLEBONDSMASS
NUMBERVARCHAR2(40)NUMBERNUMBERNUMBER(9,3)
<pk><fk>
LIPID_ASSIGNMENT
LIPID_IDTIMECOURSE_ID
NUMBERNUMBER
<pk,fk2><pk,fk1>
LIPID_HEAD_GROUP
HEAD_GROUP_ABBREVHEAD_GROUP_NAME
VARCHAR2(40)VARCHAR2(120)
<pk>
MS_EXPT
EXPIDMS_MODE
VARCHAR2(52)CHAR(4)
<pk>
MS_RESULTS
MS_IDTIMEPOINTSCORETIMECOURSE_ID
NUMBERNUMBERNUMBERNUMBER
<pk>
<fk>
MS_TIMECOURSE
TIMECOURSE_IDEXPIDMEASURED_MTOZ
NUMBERVARCHAR2(52)NUMBER(9,3)
<pk><fk>
LIPID MAPS: Data Collection
• Experimental data:
• Other MS instruments• Need to have examples of data formats
• Microarray Data
• Other experimental data
LIPID MAPS: Data Collection -Networks
• Collection of genes, proteins and other elements involved in lipid metabolism, signaling and structural frameworks
• Adapting in-house gene and protein annotation pipelines for use in LIPID MAPS
• Compilation of current information on known pathways and networks– GO (http://www.geneontology.org)
– KEGG (http://www.genome.ad.jp/kegg/)
• Experimental data emerging from LIPID MAPS consortium
LIPID MAPS: Data Presentation• Web –based interface
– LIPID MAPS website: http://www.lipidmaps.org
• Use of web –browser plugin to view/query chemical structures (also a Java-based option)
• Browser forms-based query builder:– Query chemistry, gene, protein, pathway data– Query and analyze MS, microarray experimental data– Link to other informatics tools/websites, e.g. SDSC Biology
Workbench
LIPID MAPS: Chemistry Tools (under development)
LIPID MAPS: Structure Search
LIPID MAPS: Retrieve Results
LIPID MAPS: View Structures (Chemdraw Plugin)
LIPID MAPS: Text Search
LIPID MAPS: Text Search-contextual menus
LIPID MAPS: Text Search results
LIPID MAPS: Structure Editing interface
LIPID MAPS: Pathways/Networks Presentation• Parts lists
• Function
• Sub-cellular location
• Functional domains
• Pathways
• Interactions
AFCS Example: Pathways/Networks Display
LIPID MAPS: Bioinformatics Challenges• Establishment of consistent classification, nomenclature and
structure-display for lipids
• Automation of experimental data transfer and assimilation from core sites– Dealing with non-standard/legacy experimental data
• Mining of highly heterogeneous public sources for data regarding lipid pathways, networks and interactions
• Maintaining, updating, synchronizing lipidomics knowledge base
