HMS LINCS Database - Tutorial              

(updated 2013-11-18)

This document provides a tour through the HMS LINCS Database (http://lincs.hms.harvard.edu/db/).  

It is a “learn by example” guide where we show some of the functionality of the interface.

Overview

The HMS LINCS Database has a web interface that provides access to the reagents (small molecule perturbagens, cells, and proteins, etc.) as well as for the experimental datasets of the HMS LINCS project.   Please see the LINCS  project Data Standards page (http://www.lincsproject.org/Data/data-standards/) for more information on the metadata being stored.

The HMS LINCS Database can also be accessed through the programmatic API, using the information given in the HMS LINCS Database URL Scheme and Access Guide. The second section below provides examples of usage of the programmatic interface.

1. Web Interface tutorial methodology:  

  1. Global search
  1. The global search performs a text search through all of the metadata for the different  reagents and experiments recorded in the HMS LINCS DB.
  2. To access the global search, use the “Search all categories” field at the home page.
  3. Search for “roscovitine”: http://lincs.hms.harvard.edu/db/?search=roscovitine
  1. Results in two hits:
  1. Screen HMSL20124: because the search string matches text in the title: “Roscovitine KINOMEscan”
  2. Small Molecule HMSL10001-101: because the name matches the search text.
  1. Small Molecules 
  1. Search and filtering:
  1. Select the “Small molecules” link on the left and enter search terms in the search box.
  2. To filter results by the types of bioassays performed, select the down arrow on the left side of the search box to expand the filters section. Select a bioassay type and submit.
  3. Result: http://lincs.hms.harvard.edu/db/sm/?search=&extra_form_shown=true&dataset_types=KINOMEscan
  1. Text based search:  “neratinib” (HMSL10018)
  2. Result: HMSL10018
  1. The detail information section at the top shows the chemical structure information and provides links to external listings for the compound (PubChem, ChEBI, ChEMBL, LIFE).
  2. The Nominal Targets section brings in the results of the literature review (dataset HMSL20000), for this compound it indicates that Sorafenib is an inhibitor of B-Raf and KDR.  
  3. The KINOMEscan image is shown next.
  4. The Batch Information section provides detail for each batch of this compound that is tracked in the HMS LINCS DB.
  1. Clicking on one of the batch information links expands that section to include specific batch information (provider, catalog id...).
  1. Orthogonal information about which studies have included this compound can be seen by scrolling to the bottom of the detail page and viewing the “Datasets” table.  
  2. Sorafenib (HMSL10008) is of interest because it has been annotated in both the KiNativ and the KINOMEscan studies, as well as being further studied in a MGH (CMT) Growth Inhibition Assay.  
  3. Neratinib (HMSL10018) is the subject of a KINOMEscan dataset, and also has been studied in a MGH (CMT) Growth Inhibition Assay.
  1. Structure Search: search for small molecules using structure information.
  1. Searches are performed using the PubChem Structure Search service.  This service allows the PubChem Compound Database to be queried by chemical structure or chemical structure pattern.  Matches in the PubChem database are cross referenced to the HMS LINCS DB using PubChem Compound identifiers (CIDs).
  2. Input can be in the form of a SMILES string or an sdf file (molfile).
  3. Search Modes:
  1. Identity: search for identical structures (same tautomer).
  2. Similarity search for similar structures (2D Tanimoto equation). See Pubchem Identity and Similary Search Help.
  3. Substructure: search for a for particular chemical structure pattern. See Pubchem Substructure Search Help.
  1. Example: Using SMILES: CC(N1C=NC2=C1N=C(N[C@H](CC)CO)N=C2NCC3=CC=CC=C3)C
  1. Choose “Identity” base searching
  2. results in HMSL10001 (Roscovitine) being displayed
  1. Cells
  1. Search term: 1st: “IA-LM” (50017); 2nd: “HEC-1” (50014) (HEC-1)
  2. Discussion: HMSL50017
  1. The top section gives detail information about the cell line: provider and provider catalog identifier, host organism and organ, as well as disease information, genetic information, culture conditions, and literature references for mutations, if available.
  2. The bottom section lists orthogonal information about which studies use this cell line in their assay (Moerke 2 Color Apoptosis, Tang Proliferation/Mitosis, MGH (CMT) Growth Inhibition Assays).
  1. Proteins
  1. Search term: 1st: ABL1 (200002); 2nd: AKT1 (200034, 200482, 200637)
  2. Discussion: search for “ABL1” finds ABL1 and all ABL1 mutants (27 records total, 25 KINOMEscan and 2 KiNativ).
  3. Discussion: search for AKT1 brings up 3 records (KINOMEscan, KiNativ, protein target).
  1. Datasets
  1. Search term: “apoptosis”
  2. Discussion: this results in 3 datasets, including  1 Tang datasets: “HMSL20003 - Tang Mitosis/Apoptosis ver.II”.  
  3. Clicking on 20003 gives the detail view for this dataset.  The dataset detail pages consists of the detail view as well as separate tabs for (where they exist) “Small Molecules studied”, “Cells studied”, “Proteins studied”.  Additionally, there will always be a “Results” tab.         
  1. Details tab
  1. Dataset lead investigator and lab.
  2. Summary and protocol information.
  1. Small Molecules Studied, Cells Studied, Proteins studied tabs
  1. Each of these tabs shows a table with the respective entity for this assay only.
  1. Data Columns tab:  information about each  of the data columns in the experimental result data including detailed description, units, and readout type.
  2. Results
  1. Experimental result data for this assay:
  1. Information for each result: the small molecule batch used, the cell line tested, and the protein information, if applicable.   Additional information such as the library plate and well can be found in later columns.
  2. Experimental result data:
  1. Microscopy images (via the OMERO server).
  1. Note: additional navigation and features are available in the OMERO interface (e.g. see “split channel” view).
  2. Image downloads: see “5. Microscopy Images” section below.
  1. Derived information: cell counts, cell phenotype counts.
  1. Filtering of results displayed/downloaded:
  1. select the “filter results >>>>” link
  2. results with Small Molecules  HMSL10041, HMSL10062,  and Cell HMSL50001 chosen: http://lincs.hms.harvard.edu/db/datasets/20003/results?small+molecules=44&small+molecules=65&cells=1
  1. Microscopy images are provided with the dataset views (via the OMERO server).  To obtain complete the complete set of images for a dataset, please contact Jay_Copeland @  hms.harvard.edu

2. Programmatic API usage:

  1. Top level:
  1. List of endpoints: http://lincs.hms.harvard.edu/db/api/v1/?format=json
  1. Entity listings:
  1. List Small Molecules: http://lincs.hms.harvard.edu/db/api/v1/smallmolecule/?format=json&offset=10&limit=30
  2. List Cells: http://lincs.hms.harvard.edu/db/api/v1/cell/?format=json&offset=10&limit=30
  1. Note, we have set and “offset” and and “limit” to restrict the size of the returned data.
  1. Other:
  2. Proteins: http://lincs.hms.harvard.edu/db/api/v1/protein/?format=json
  1. Dataset:
  1. Detail: http://lincs.hms.harvard.edu/db/api/v1/dataset/20120/?format=json
  2. Experimental result data (SAF format -- used for data interchange with the University of Miami LIFE system): http://lincs.hms.harvard.edu/db/api/v1/datasetdata/20120/?format=csv
  1. Display a single entity by HMSL ID:
  1. Cell: http://lincs.hms.harvard.edu/db/api/v1/cell/50008/?format=json
  2. Small Molecule: http://lincs.hms.harvard.edu/db/api/v1/smallmolecule/10009-101/?format=json