CRISPRbrain is live! A data commons for functional genomics screens in differentiated human cell types.

We are very excited to announce the launch of CRISPRbrain.org!!!

CRISPRbrain is an amazing resource for functional genomics screens in human cell types. This data commons is laying the #openscience foundation for a ton of high-throughput unbiased screens in the future. Its goal is to organize and standardize results from such screens carried out by different research groups, and to enable users to explore, visualize, and compare them. 

We are very proud of how CRISPRbrain came to be. It was a unique collaboration between Data Tecnica International and the Kampmann Lab (UCSF), developed by the scientists, for the scientists. The team put a lot of thought into what information and analytics scientists could benefit from. Talking about teamwork, the Kampmann Lab team from UCSF really set the new standard for scientific/engineering collaboration and providing feedback to analysts and developers (they were amazing, positive vibes all around).

Current functionalities 

CRISPRbrain currently features screens with “simple” readouts (such as survival and fluorescent reporter levels), as well as screens with complex readouts (such as transcriptomes). Screens can be browsed and searched based on parameters of interest, such as cell type, genotype, mode of CRISPR perturbation, screen method and phenotype, as well as a full-text search (Figure B).

For simple screens, the phenotypes for the perturbed genes can be displayed as volcano plots and rank plots (Figure C). Data points can be selected individually or in groups to display information about the perturbed gene(s). Gene names can be entered to label them in the graph. Data for the entire screen or for selected genes can be exported for offline analysis. Two screens of interest can be compared in a scatter plot (Figure D).

For RNA-Seq-based screens, genes of interest can be selected to display the transcriptomic phenotype resulting from perturbation of the gene (Figure E). Individual data points can be selected to display information about the transcript, and underlying data can be exported for offline analysis. Alternatively, the results from the entire screen can be explored in a hierarchically clustered heatmap of RNA-Seq phenotypes (Figure F).

Here is a quick snapshot of the site from Ruilin’s paper.

CRISPRbrain design and development 

CRISPRbrain is developed as an open-access and cloud-based platform striving to make data and code easily accessible to the scientific community. To enable scientific transparency and replication, each dataset in CRISPRbrain is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). 

To handle a large volume of storage and computation demand, CRISPRbrain is deployed on the cloud with elastic resource allocation. We have prioritized a low-latency interactive user experience by pre-computing and caching complex queries. CRISPRbrain is implemented in a manner that is “future-proof”, supporting scalability and addition of more complex features.

This is really the baseline for a growing set of tools and data hosted by CRISPRbrain. One thing that stands out besides just the functionality, is the design, clarity, and ease of navigation … This really speaks to me, because if you can’t find the info or don’t want to look at how it’s presented, why use a resource in the first place?

Preprint 

The manuscript (in preprint) clearly and concisely explains the first genome-wide CRISPRi & CRISPRa screens in human neurons. It finds a surprising role of PSAP in neurons, but not other cell types. In neurons, these edits at PSAP kick off a deficiency in the formation of lipofuscin, a hallmark of aging and many degenerative diseases, triggering ferroptosis, a type of cell death. Neurons, one of the longest-living cell types in the human body, are challenged by various stresses in aging/disease. Neurons do not have the ability to 'self-renew' by cell division. So, robust stress response mechanisms are required for neurons to maintain long-term health. Findings suggest that inhibiting lipofuscin formation or subsequent ferroptosis may serve as new therapeutic strategies for these diseases. You can really see how this has the potential to influence drug dev in years to come.

Ruilin Tian, Anthony Abarientos, Jason Hong, Sayed Hadi Hashemi, Rui Yan, Mike A. Nalls, Andrew B. Singleton, Ke Xu, Faraz Faghri, Martin Kampmann. (2020). Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. bioRxiv 2020.06.27.175679; doi: https://doi.org/10.1101/2020.06.27.175679

Future 

One thing to keep in mind is that CRISPRbrain is a foundational data commons for the future, so your feedback is really important. If you liked (or hated) what you saw on the site, let us know by leaving some feedback! Thanks for taking the time to check it out. We also invite all research groups to contribute their functional genomics datasets to CRISPRbrain, with the ultimate goal to build a comprehensive atlas of gene function in all human cell types.

Future versions of CRISPRbrain will support other high-dimensional phenotypes, such as imaging and electrophysiological data, and enable cloud computing and machine learning, thus providing researchers with a suite of tools to process, visualize, analyze and contribute functional genomics screening data in different human cell types. Parallel genetic screens across the full gamut of isogenic human cell types will uncover context-specific roles of human genes, leading to a deeper mechanistic understanding of how they control human biology and disease.

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Blogged by Mike N. with some help from Faraz F.