Candidate target validation
Does perturbing the target change a disease-relevant phenotype, and what supports further investment?
Target discovery services · Functional genomics
Target discovery with PDO 1.0 & PDO 2.0
From genetic library screening to hit validation, investigate disease mechanisms, drug response and microenvironmental function to prioritize targets for further research.
- Library screeningGenes, pathways & controls
- Hit confirmationIndependent perturbation & molecular checks
- Functional validationGrowth, structure & immune function
- Target prioritizationResponse, mechanism & R&D decision
R&D decisions
Design models, screening and validation around your next R&D decision
Dependencies & synthetic lethality
Which genes may be required in a defined molecular background, and how selective are those dependencies?
Resistance mechanisms & combination hypotheses
Which changes accompany resistance, and which interventions merit combination studies?
Immune-regulatory target exploration
How could perturbations in tumor or immune cells affect recognition and killing, and which models and readouts can test those effects?
PDO 1.0 + PDO 2.0 · Complementary research platforms
From tumor-intrinsic mechanisms to microenvironmental function
Either platform can provide a starting point for target research. Match models, perturbations and functional readouts to the question, with standalone studies or discovery and validation across complementary systems.
PDO 1.0
Explore tumor-intrinsic dependencies
Design candidate-gene validation, genetic library screening and resistance studies around tumor-cell growth, survival and drug response, connecting targets to tumor phenotypes.
Compare PDO 1.0 and PDO 2.0 ↗PDO 2.0 / ALI
Explore microenvironment-associated targets and functions
Use tissue architecture, immune composition and molecular features to frame microenvironment-associated target hypotheses and design studies of tumor–immune interactions, immune recognition and killing, and drug response.
Explore PDO 2.0 / ALI ↗Connecting the platforms
Frame hypotheses from disease and molecular context, screen candidates in the model and assay context that fits the question, and connect PDO 1.0 tumor phenotypes with PDO 2.0 microenvironmental readouts for functional validation and target prioritization.
Genetic library screening & target prioritization
Genetic library screening in organoids
Design organoid perturbation and library-screening studies around disease mechanisms, drug sensitivity and resistance. Connect molecular features, functional phenotypes and independent validation to discover and prioritize candidate targets.
- 01
Select models
PDO 1.0 / PDO 2.0
Match the research question - 02
Design libraries
Genes, pathways & controls
Define screening scope - 03
Perturb genes
Delivery & perturbation checks
Establish study groups - 04
Analyze the screen
Sequencing or phenotype
Prioritize candidate hits - 05
Validate targets
Tumor & microenvironment readouts
Inform R&D decisions
Comparison design
Control condition↔Drug-treated or study condition
Connect perturbations with growth, survival and drug response to identify candidates for validation.
Target discovery & disease dependencies
Design focused libraries around disease-associated pathways or candidate gene sets to identify potential dependencies affecting organoid growth and survival.
Resistance & combination targets
Compare perturbation effects between drug-treated and control conditions to explore sensitivity, resistance mechanisms and combination strategies.
Functional validation of screening hits
Plan independent perturbations, molecular confirmation, functional assays and validation in additional models to inform target prioritization.
We work with you to define the library scope, screening scale, controls and sequencing or phenotypic readouts around your target genes, organoid models and available data. CRISPR or RNA interference can be selected to fit the research question.
Discuss a library-screening study ↗TRiCBIO study results
How these study results support target discovery
01 · Target-informed model selection
Select matched samples for target research
Under the same staining conditions, candidate tissues show different TGF-β1 expression levels.
Use this comparison to select samples for follow-on PDO drug-response and mechanism studies.
View image02 · Gene delivery and expression
Gene delivery and expression in HCC organoids
Comparing organoid morphology and expression signals under scramble shRNA and lncRNA shRNA conditions informs experimental conditions for molecular confirmation and functional studies.
Explore gene delivery and perturbation studies ↗Scramble shRNA
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View imagelncRNA shRNA
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View image03 · Cellular and molecular context
Use paired single-cell profiling to select study endpoints
Paired single-cell profiling of liver cancer tissue and a PDO identifies T-cell-related groups, B cells, macrophages and other populations available to support immune-associated target research.
Use that cellular context to select readouts for mechanistic studies and drug evaluation.
Source tissue
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View imagePatient-derived organoid
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View imageTeam research foundation
Move from genomic clues to functional validation
A Nature Medicine study involving a member of our team shows how candidate function can be tested: compare Igf2, miR-483 and their combination in Apc-deficient mouse colon organoids, then use histology, proliferation and invasion results to assess candidate driver function.
Li et al., Nature Medicine, 2014 · Fig. 5 ↗Project deliverables
- Project plan: model selection, perturbation strategy, experimental groups and quality criteria.
- Project data: perturbation confirmation, functional assay data and candidate-target ranking.
- Validation and recommendations: confirmation of key candidates, mechanistic interpretation and next-development priorities.
Ways to work together
Contract research & R&D collaboration
Contract research services
Tailor models, screening and validation to your targets, drug candidates and R&D questions, with experimental data, analytical reports and recommendations for follow-up studies.
Discuss a target-discovery project ↗Joint discovery & validation
Combine complementary models, data, technology and drug candidates to discover and validate targets, investigate mechanisms and advance promising research programs.
Discuss R&D collaboration ↗Building on target evidence and drug-candidate research, explore a collaborative path from joint discovery and functional validation toward drug co-development.
Field developments
Public studies are expanding organoid target discovery
Three peer-reviewed Nature studies published in August 2026 highlight practical directions for study design: larger patient-derived model resources, genome-wide CRISPR screening in organoids, and dependency maps that include additional cancer subtypes and cell states.
These public studies use patient-derived organoids, spheroids and other patient-derived cancer models, offering references for model coverage, screening scale and hit validation. For client studies, PDO 1.0 can address tumor-intrinsic dependencies; PDO 2.0 can be considered when tissue architecture, immune context or microenvironmental function matters.
- A compendium of next-generation patient-derived models for diverse cancers ↗Nature
A resource of 665 patient-derived models across 25 cancer types, linked to clinical and multi-omic annotation for functional research.
- A tumour-derived organoid biobank maps cancer gene dependencies ↗Nature
A biobank of 256 characterized tumor organoids, with genome-wide CRISPR screens across 162 models mapping cancer dependencies.
- A dependency map enhanced with next-generation 3D cancer models ↗Nature
A set of 147 genome-wide CRISPR screens in organoids and spheroids across 10 cancer types, extending DepMap to new molecular subtypes and state-associated dependencies.
Project discussion
Questions clients ask about target discovery
What information can start a target-discovery project?
An initial discussion can start with non-confidential disease context, candidate targets, available models or data, and the R&D decision this stage needs to support. The team can then discuss models, perturbation strategy, controls, readouts and a validation approach.
Can target studies use both PDO 1.0 and PDO 2.0?
Either platform can be used on its own, or the two can be connected when the research question benefits from both. PDO 1.0 supports tumor-intrinsic dependency, growth, survival and drug-response studies; PDO 2.0 can extend the work into tissue architecture, immune context and microenvironment-associated function. The study design depends on model conditions and intended readouts.
Can target discovery proceed as contract research or joint R&D?
Yes. Contract research can tailor models, screening and validation to defined targets, candidates and R&D questions. Joint R&D can combine complementary models, data, technology or candidates for shared discovery and functional validation. Roles, data use, intellectual property and follow-on arrangements are defined in the applicable collaboration documents.
Start with your target-discovery needs
For the initial discussion, share non-confidential disease context, candidate targets, available models or data, and the R&D decision you need to support.
Discuss a target-discovery project