Collaborate With Us
PRISM has worked with 200+ collaborators from academic institutions, pharmaceutical companies, and biotechnology startups. Over 29,000 compounds have been screened in 500+ PRISM cell lines since 2015. Please review the details of our process below and send us a message if you’re interested in collaborating with us:
We do not offer a Fee-for-Service model for PRISM. We work with collaborators on scientifically engaging projects as part of a collaboration. Key points of collaboration include:
Compound structures do not need to be shared
Data may be published only when the collaborator agrees
Intellectual property will be jointly filed on jointly discovered inventions
PRISM projects typically fall into one of three categories which offer different degrees of customization:
Shared Screens:
Users may submit a small number of compounds (<40) to be run against our current cell panel. As a standard, each compound is run at 8 pt. dose with 3-fold dilutions in triplicate.
Our shared screens are designed to share resources and reagents in order to keep costs down. Since compounds from multiple submitters are run on the same plate, these shared high-throughput assays necessitate using a single, standardized workflow.
Submitters simply need to choose your top screening dose and submit a 1000x stock solution in DMSO.
Cell sets are not customizable.
Combination Screening:
Compound Selection:
At this time all compounds used in combination screening are required to meet all of the same guidelines as our shared screens (compounds must be soluble in 100% DMSO and submitted as 1000x stock solution).
Study Design:
Similar to our shared study design for single-agent screening, we are only currently offering collaborators one study design for combination screening.
All combinations will be run in the following format:
Drug A at dose (7 pt. dose with 3-fold dilutions) alone
Drug B at one anchor dose alone
Drug A at dose (7 pt. dose with 3-fold dilutions) plus Drug B at one anchor dose
This screen of Drugs A and B counts as two ‘compound slots’ in our PRISM assay.
Dose Selection:
Combination screening requires careful selection of doses which can be especially difficult in a pooled context. Therefore we only recommend using this assay for compounds with previous validation and/or known dosing.
When selecting an anchor compound/dose we aim to choose the maximum dose that does not broadly affect cell viability but gives a reproducible phenotypic effect in a specific cell line or set of cell lines.
Data Analysis:
At the end of a combination screen, users will receive three standard PRISM reports:
Standard analysis of compound at dose and anchor separately
Standard analysis of combination
Standard analysis of the differential response between single compound and combination (determined by subtracting log-fold change values and by taking the ratios of AUC and IC50)
Custom Projects
Anything that falls outside our standard shared screen protocol including aqueous compounds.
Projects include large screens (>1000 compounds) against our standard PR500 cell lines
Collaborators may select timepoint (up to 5 days), top dose and number of doses, biological replicates.
How long does the assay take to run?
Data release occurs approximately 3 months after the compound submission deadline. If for any reason we are unable to meet that deadline, we will let you know as soon as possible. If you don’t hear from us while the assay is running that means everything is proceeding on-time! Our typical assay workflow is as follows:
Once all compounds have been received, we make them into Assay Ready Plates using the Broad Institute’s Compound Management group’s automated liquid handling capabilities (~2 weeks)
Next, we add the cells directly on top of the compound in 384-well plates. We use two cell sets (PR500, PR300+) which each undergo a 5-day treatment (~2 weeks)
After cell treatment, we lyse the cells, amplify the barcodes, and detect them using a bead-based Luminex system (~4 weeks)
We then undergo a standard data processing pipeline with extensive QC (~4 weeks)
Upon screen execution and completion, the following data will be shared:
Normalized cell viability: log fold-change (LFC) normalized to plate control (LFCPC) or vehicle control (LFCVC)
IC50 & AUC data for compounds tested at the established doses.
Results of one or more genomic feature association analyses
Any other agreed upon analysis
What criteria must a compound meet to be screened in PRISM?
We screen compounds at all different stages of optimization.
The user is responsible for ensuring that the compound is soluble in 100% DMSO at the stock concentration. Compounds that are submitted without structure information cannot be QCed, and the user is responsible for QC of their compound prior to submission.
For compounds with stability/solubility issues we would strongly suggest trying to recreate the stressors of the PRISM protocol in-house prior to submitting. If you would like to take the next several months to run additional optimization and QC on your compound to ensure it will perform well in this type of high-throughput screen, we offer screens approximately every three months. Unfortunately we don’t have the bandwidth to do any optimization for, or re-running of compounds that don’t perform well in PRISM. Any compounds submitted will be run ‘at-risk’.
When can I submit a compound for screening?
The PRISM team currently runs shared screens approximately once per quarter. Submission deadlines will be announced on the PRISM website at least a month in advance. These month-long submission windows are the only times we accept compounds for shared screens.
Please allow adequate shipping time for the PRISM team to receive the compounds by the submission deadline. To prevent delays for other users, any party unable to meet the submission deadline will be pushed to the next scheduled run.
How much compound do I need to provide?
Compounds must be provided as a stock DMSO solution. We require at least 150μL of 1000x the desired screening concentration in 100% DMSO.
For example, if you submit for 8-point dose screening and your starting concentration will be 10μM, you will need to submit at least 150μL of 10mM stock.
How do I submit a compound for screening?
Make sure to fill out the Compound Submission Form completely before shipping compounds. Please contact PRISM@BroadInstitute.org for the form.
Provide funding information (if applicable) before shipping.
Include shipping/drop-off information.
Make sure your compound vial(s) are clearly labeled with your name, compound name, and volume/concentration. The user is responsible for ensuring that this is accurate.
Ensure your vial(s) are securely packaged and on dry ice (if necessary).
Follow the appropriate shipping instructions for either domestic or international shipments. International submitters with questions about shipping please reach out to us for our broker’s contact information (Please DO NOT ship your compounds directly to the broker).
All submitters must email PRISM@BroadInstitute.org with tracking information so we can ensure someone will be available to receive and properly store your compounds.
