Cheat sheet: High-Throughput Screening

Description

High-throughput screening (HTS) involves automated testing of chemical and/or biological compounds against a target, typically biological. The process is automated through the use of microwell plates and/or microarrays, robotics, liquid handling, data processing, and sensitive detection systems. The detection systems are typically optical plate reader data, imaging data, or flow cytometry data.
Screening data generated in Norway are collected using a large quantity of compounds from diverse suppliers that are tested against a variety of targets in many different assay types using various detection methods. Such heterogeneities make unifying HTS data generated in Norway an ongoing challenge.

Type of data/experiments/methods

Plate reader data as text files

Multidimensional image data (High content screening - HCS)

Open Microscopy Environment - Tagged Image File Format (OME-TIFF)
Open format

Flow Cytometry Data

Flow Cytometry Data File Standard (FCS)
XML-based gating definitions (Gating-ML)
Open format

Metadata Standards

Standards

Ontologies

General:
EU-Openscreen-specific:
Imaging-specific:
Flow Cytometry-specific:
- Ontology for Biomedical Investigations (OBI)
- Cell Ontology (CL) for cell types

Sources for Reusable Data

PubChem BioAssay

Small-molecule and RNAi screening data
Citation guidelines (No usage license)
Identifiers:
- Resource unique identifiers for single chemical structures (CID), substances (SID), and assays (AID)
- Other identifiers:
  - Targets (genes/proteins): NCBI Gene IDs/NCBI Protein accession IDs
  - Taxonomy: NCBI Taxonomy ID, the common name, or scientific name of an organism
  - Pathways: integrated from various sources and identified by SOURCE:ExternalID
  - Patents: for chemicals mentioned in a patent, unique patents identified by patent number (e.g. US5969156)
How to access BioAssay data

ChEMBL

Manually curated database of bioactive drug-like small molecules
CC BY-SA 3.0 License
Identifiers:
- Resource unique identifier (ChEMBLID) for compounds, targets, assays, documents, tissues and cell types in ChEMBL
- ChEMBLIDs for molecules can be converted to many other identifiers via UniChem
Access via web interface or download data directly

European Chemical Biology Database (ECBD)

Small molecule screening data generated within the EU-OPENSCREEN network
CC BY 4.0 License
Identifiers:
- Resource unique identifier (EOS#) for assays, compounds, and targets
- InChIKey as unique compound identifier
- Additional identifiers for compounds: PubChem CID, MolPort number, and if available: ZINC, Mcule, eMolecules identifiers
Search the database from a web interface or download the data directly

IDR

A public repository for reference imaging datasets. Research community can submit search and access the raw datasets.
usually CC0 or CC BY 4.0
Identifiers:
- DOI
- See also: Ontologies
- Other identifiers: Targets (genes/proteins): Gene IDs/UniProt Protein accession IDs
Access possible through API and direct download, you can run image analysis workflows directly on IDR datasets on usegalaxy.no using the IDR download tool

Storage and Computing

HTS data collected in Norway are analyzed and stored at individual screening sites in NOR-Openscreen.
Metadata for screens run in Norway will be compiled into a central database.

Data Deposition Repository

PubChem BioAssay

Data submission policy (no license available)
Identifiers:
- CID for unique chemical structures
- SID assigned to each record (substance or annotation) submitted, can be associated to multiple CIDs
- Experiments submitted on different substances are assigned unique BioAssay identifiers (AID)
Submit chemical structures, annotations, and bioassay results
Embargo for up to 1 year

ChEMBL

CC BY-SA 3.0 License
Identifiers:
- Data depositor (source) assigned unique src_id
- Depositor-defined Identifiers (DDIs) are used for Compounds/Substances (CIDX), Assays (AIDX) and References (RIDX)
Submission by e-mail request to chembl-help@ebi.ac.uk
- Data sets deposited in ChEMBL are incorporated into PubChem
- Check the ChEMBL Loader documentation if your data are suitable for deposition

Ethics and Regulations

Patient Data

Pre-approval for medicinal/health-related research projects from the Regional Ethics Committee is required
Projects handling personal data are assessed at many institutions by SIKT
Otherwise data must be fully anonymized - neither directly or indirectly identifiable to an individual

Services in Norway

NOR-Openscreen is the research infrastructure for high-throughput screening and bioprospecting in Norway.
The four nodes of NOR-Openscreen in Oslo, Bergen, Trondheim, and Tromsø provide various chemical biology services.
Research data is managed at individual sites and coordinated at the RI-level.

RDM Services

For help with management of high-throughput screening data please contact alexandra.gade@ncmm.uio.no

Scientific Services

Chemical Biology Platform at NCMM/UiO
- Chemical biology and high-throughput screening services
- chembio@ncmm.uio.no / Website Link
Biophysics, structural biology, and screening (BiSS) at UiB
- Core facility for studing the interactions of small molecules with macromolecules, protein biophysics, and for crystallization.
- biss@uib.no / Website Link
High throughput Screening at SINTEF Biotechnology and Nanomedicine
- High-throughput screening services specialized in microbial cultivation, enzyme evolution, and mass spectrometry
- Geir Klinkenberg / Website Link
Marine Bioprospecting (Marbio) at UiT
- Analytical platform for natural products
- Jeanette Andersen / Website Link