Human Cell Atlas

 

Nature | Comment, 26 October 2017, p.451

The Human Cell Atlas: from vision to reality

Orit Rozenblatt-Rosen, et.al.

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An international collaboration between hundreds of scientists from dozens of universities and institutes — including the UK Wellcome Trust Sanger Institute, RIKEN in Japan, the Karolinska Institute in Stockholm and the Broad Institute of MIT and Harvard in Cambridge, Massachusetts — aims to create comprehensive reference maps of all human cells as a basis for research, diagnosis, monitoring and treatment.

New technologies offer an opportunity to build a systematic atlas at unprecedented resolution. These tools range from single-cell RNA sequencing to techniques for assessing a cell’s protein molecules and profiling the accessibility of the chromatin. For example, we can now determine the RNA profiles for millions of individual cells in parallel. Protein composition and chromatin features can be studied in hundreds or thousands of individual cells, and mutations or other markers tracked to reconstruct cell lineages. We can also profile multiple variants of RNA and proteins in situ to map cells and their molecules to their locations in tissues.

The first draft of the atlas will profile cells’ molecular and spatial characteristics, capturing only those cell types that occur above a pre-specified rarity.

The atlas will aim to provide a detailed representation of molecules, cells, tissues, organs and systems, allowing researchers to zoom in and out to identify patterns and interactions at various levels of resolution. To this end, those compiling the atlas must establish how many cells to sample, which types of molecular features to analyse, how to assign cells to different categories and how to subdivide those categories. At the spatial level, they must decide how to sample complex anatomies and histologies. Lastly, they need to establish ways of connecting the various layers of cellular and spatial information from different samples to a single anatomical reference by developing what is termed a common coordinate framework

Atlas data and analysis products will exist in multiple public clouds (currently, those hosted by Google, Amazon and Microsoft) to ensure that people with different preferred cloud environments can access them. Because computation will happen in the cloud, individual researchers will not need to download and store all the data or have access to their own high-performance computing power. Finally, in addition to the continual release of data and periodic formal data releases, publications interpreting the data will help to establish standardized approaches and disseminate the insights and value that can be gained from them. 

A technical forum involving genomics experts, imaging specialists and biotechnologists, is developing new technologies, and testing, comparing and disseminating existing ones. A data-coordination platform is being designed to bring researchers to the data by developing the software to upload, store, process and serve data. The platform also provides an open environment in which computational methods and algorithms developed by any interested group can be shared. Finally, an analysis garden involves computational biologists working together to develop sophisticated techniques for data mining and interpretation.

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