Building a high-quality Human Cell Atlas.

Abstract

To the Editor — Building the Human Cell Atlas (HCA) requires consistent and agile experimental designs, standardized operating protocols (SOPs), benchmarks and quality control metrics that can adapt to a rapidly evolving technological landscape. Here, the HCA Standards and Technology Working Group outlines pertinent technical challenges and their approach to defining benchmarks and quality control measures to ensure high-quality data for building a comprehensive and accurate human cell atlas and help guide other atlas projects in health and disease. The HCA aims to create comprehensive reference maps of all human cells, the fundamental units of life, as a basis for both understanding human health and diagnosing, monitoring and treating disease1. By integrating single-cell resolved molecular profiles of tissues and organs, it seeks to generate cellular and spatial maps, including the identification of dynamic cell states and rare cell populations. This effort requires the generation of high-quality data in multiple laboratories around the world, first assembled as a draft atlas and then increased in resolution and breadth by continued contributions from the community over time. The HCA community is open and collaborative, sharing its data through an open-source data coordination platform (DCP; https://www.humancellatlas. org/data-coordination/) and bringing together and aligning biological, clinical, computational and engineering experts from diverse fields. Since the HCA’s launch in October 2016, more than 1,700 scientists from across the globe have enthusiastically joined to help shape this effort, through scientific collaboration, planning meetings, computational jamborees, social media and funding calls. Dedicated participants have formed biological networks spanning organs and systems, established their scientific leadership, and rapidly embarked on large scale data collection and analysis to build draft atlases. As data collection for the HCA spans labs and techniques, spanning years and many technical innovations, it requires careful experimental design to construct a cohesive atlas. The HCA community is committed to producing the highest quality data possible and establishing rigorous standards, shared openly and broadly and updated regularly, ensuring findable, accessible, interoperable and reusable (FAIR) data principles2. The HCA develops, adopts and shares new tools for comprehensive and multidimensional atlas production. It also maintains flexibility, so it can revise the design of the HCA production and analysis as new insights, data and technologies emerge. Design considerations include both the choice of existing data-generating technologies and efforts to develop and assess new technologies with more measurement capabilities, increased scale and/or lower cost. Thus, benchmarking HCA data and technologies is a priority both for the HCA initiative and more broadly for the single-cell genomics field — including related efforts in specific disease areas or model organisms, such as the BRAIN Initiative Cell Census Network (BICCN), the Cancer Moonshot Human Tumor Atlas Network (HTAN) and LifeTime. To fulfill this mission, the HCA established a Standards and Technology Working Group (STWG) not only to guide and advise its members around technology choices but also to outline best practices and help coordinate and carry out scientific work to support this mission (Fig. 1). The STWG encompasses 18 members from 14 institutions across 7 countries, spanning diverse areas of expertise. The STWG initiates and leads efforts to compare, test and benchmark existing methods, the deployment of new methods and the development of analytics and quality control measures.