Platforms
High Throughput Phenomics
Introduction
High Throughput Phenomics platform (HTP) enables, High Content Screening (HCS), that combines automated imaging and quantitative data analysis in a high-throughput format suitable for large-scale applications such as drug discovery and systems biology utilising high throughput image phenotyping.
HTP support medium-scale high throughput/content screening campaigns. HTP hold diverse targeted small molecule probes/libraries and genome wide siRNA/shRNA libraries in 384-well Ready-To-Screen format. Overall, HTP can provide novel systems-level insight for your complex biological questions.
Key Expertise
High Content Screening
3D Spheroid Characterisation
High Content Analytics
Heterogeneous Co-culture Modeling
Cell Painting
Image-based Cellular Activity (Outgrowth, Migration, Localisation, Marker Expression, etc.)
Cell Painting – Detailed Morphometric Characterisation based on changes in sub-cellular components
Osteosarcoma cells were treated with small molecules and at the end of 48-hours, cells were stained for 8 sub-cellular organelles using 6 specific dyes.
Co-culture Modeling – Compounds Targeting Specific Sub-populations of Head & Neck Tumour
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DMSO Pri. (Green) and Met (Red) cells |
Compound 1 targets Pri. (Green) cells |
Compound 2 targets Met (Red) cells |
Compound 3 targets both Pri. and Met |
Primary and Metastatic Head & Neck tumour cells were co-cultured. Compound 1 selectively kills primary cells, compound 2 selectively kills metastatic cells, and compound 3 kills both primary and metastatic cells.
Marker Expression – Compounds Inhibiting β-catenin in Colorectal Tumour
High Content Screening – Nucleus (Blue) + β-catenin (Green) + Cell Marker (Red)
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DMSO Control | Compound 1 | Compound 2 |
Protein Activation – Compounds Dephosphorylating ERK in Tumour
High Content Screening – Nucleus (Blue) + pERK (Green)
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Uninduced Control | Induced Control | Induced + Compound 1 | Induced + Compound 2 |
Cellular Activity – Compounds affecting Neurite Outgrowth in Amyotrophic Lateral Sclerosis Change Negative Control to Compound 1, Positive Control to Compound 2
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DMSO Control | Compound 1 | Compound 2 |
3D Tumour Spheroid Modelling – Compounds Targeting Colorectal Cancer
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Brightfield | 3D-live cell detection-Calcein AM staining | ||||
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Brightfield | 3D-live/dead cell detection-Calcein AM/Propidium Iodide staining |
Colorectal cancer cells were grown in ULA plates for 4 days to form spheroids and exposed to small molecule treatment for 3 days. Compound 2 exhibits higher toxicity than compound 1.
HTP Technologies
State of the Art Technologies Available at HTP
a) High-content Imaging and Analysis Instruments
Our systems for high-content imaging (HCI) and high-content analysis (HCA) provide flexible scalability for your research. They feature options and modules to address your specific research including objectives, filters, imaging modes, and environmental conditions. All our systems support a wide range of applications, increased throughput, and we have streamlined workflows.
b) High-throughput Liquid Handling and Assay Instruments
At HTP, we have modular assay automation systems that provide greater flexibility in complex cell-based assay development and screening. We have state-of-the-art instrumentation, for distribution of compound or siRNA/cDNA libraries, and large-scale data analytics solutions.
Library Resources
Libraries Available in HTP (Small Molecules & Genome Wide siRNA/shRNA/cDNA)
Small Molecule Libraries for Validation/Repurposing Projects | Small Molecule Libraries for Discovery Projects | Genome-wide siRNA/shRNA/cDNA libraries |
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- Smart collection of small molecule libraries in which targets are annotated significantly, that can be used for target validation/re-purpose studies.
- Small molecule diversity sets.
- Access to SMILE structures for custom sets based on your target(s) or assay needs.
- Genome wide siRNA/shRNA and cDNA libraries for genetic manipulation studies.
- Web-based data analysis portal for pipeline analysis support for your screens-plate uniformity, %CV between your replicates and show you the top hits in waterfall graph.
Milestone Projects
Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore – A*STAR
HTP Libraries:
- Anti-cancer
- Kinase Inhibitors
Screening Objectives: To identify alternative therapeutic sensitivity to inhibitors of cell proliferation in Gefitinib-resistant cells.
- Phospho-histone H3 (S10) Status
- Target Validation with siRNA Screening
- High Content Screening
Publication: A chemical genetic screen identifies Aurora kinases as a therapeutic target in EGFR T790M negative, gefitinib-resistant head and neck squamous cell carcinoma (HNSCC). Joo Leng, et al., Jan 2021. EBioMedicine, Doi: /10.1016/j.ebiom.2021.103297
Partner Institute: Cancer Science Institute of Singapore – NUS
HTP Libraries:
- Combination Screen (Anti-cancer + Kinase Inhibitors)
Screening Objectives: To identify compounds selective for cancer cells with p53R158G mutation.
- NFĸB signaling
- Drug Combination Screening
- High Content Screening
Publication: Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation. Li Ren Kong, et al., April 2020. Nature Communications, Doi: /10.1038/s41467-020-15608-y
Partner Institute: Cancer Science Institute of Singapore – NUS, Genome Institute of Singapore – A*STAR, and Bioinformatics Institute – A*STAR
HTP Libraries:
- Natural Product extracts (21,575 compounds)
Screening Objectives: To identify compounds that reduce viability of Liver Cancer Cells expressing high levels of SALL4.
- Oxidative Phosphorylation Sensing
- High Content Screening
Publication: New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Li Ren Kong, et al., April 2020. Gastroenterology, Doi: /10.1053/j.gastro.2019.08.022
Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore – A*STAR
HTP Libraries:
- siRNA for transcription factors
- siRNA for chromatin remodelers
- ChemDiv Epigenetics
Screening Objectives: To identify the underlying epigenetic mechanism in drug-induced cellular anomalies of HN120Pri and HN137Pri primary cancer cells.
- Synthetic Lethal Screening
- BRD4 and JQ1 signaling
- High Content Screening
Publication: Longitudinal single-cell RNA sequencing of patient-derived primary cells reveals drug-induced infidelity in stem cell hierarchy. Sharma et al., November 2018. Nature Communications, Doi: /10.1038/s41467-018-07261-3
Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore – A*STAR
HTP Libraries:
- Anti-cancer
- Kinase Inhibitors
Screening Objectives: To identify compounds specifically targeting HN137-Primary / HN137-Metastatic cell population or both.
- Co-culture Modelling
- High Content Screening
Publication: Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time. Shumei Chia et al., September 2017. Nature Communications, Doi: /10.1038/s41467-017-00451-5
Services
High Content Image Based Screen |
Assay Automation and Miniaturisation Expertise |
Training |
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People @ HTP

Dr Giridhanran Periyasamy
Head-HTP
Expert in Automation and Imaging
Expert in Target and Lead Discovery

Shivaji Rikka
Research Manager
Expert in Screening Technology
Expert in Optimising Assay Biology

Matan Thangavelu T
Senior Manager
Expert in HTS and HCS Automation and Imaging
Expert in High Content Image Analysis

Yi Li Gian
Research Associate
Expert in Assay Technology and Miniaturisation
Expert in HT-Liquid Handling