WU Nephrology Integral Part in CZI Push to Accelerate Scientific Discovery

The Chan-Zuckerberg Initiative (CZI), founded by Facebook co-founder and CEO Mark Zuckerberg and his wife, pediatrician Priscilla Chan, has an ambitious goal: to help scientists cure, manage, or prevent all disease by the end of the century.

As part of that goal, in 2017, CZI funded 38 pilot projects to contribute to the Human Cell Atlas project, which is focused on creating a comprehensive, open-reference map of every cell type in the body. Washington University researchers head two of the pilot projects.

Benjamin Humphreys, MD, PhD, Joseph P. Friedman Associate Professor and Chief of the Division of Nephrology, is researching all cell types of the human kidney using single-cell RNA sequencing. Single-cell genomic analysis is a new technique that simultaneously measures the expression of thousands of genes in thousands of single cells.

Samantha Morris, PhD, Assistant Professor of Developmental Biology and Genetics, is using single-cell RNA sequencing to analyze cells in the liver and small intestine. Her project will also help with multiplexing and standardization of this new technique so that results can be compared across labs.

Drs. Humphreys and Morris recently attended a CZI investigator meeting in San Francisco, CA, hosted by Cori Bargmann, PhD, who is the president of CZI. With 38 presentations, 10 group panels, and a lot of mingling, the meeting allowed the investigators the chance to connect and foster collaborations.

“This is an exciting initiative and CZI has brought together a diverse and very talented group of investigators,” says Humphreys. “I spent the meeting scribbling new ideas into my notebook. The single cell genomics field is moving so rapidly, and I am certain it will have a major impact on our understanding of kidney diseases.”

Research partially funded by CZI from Dr. Humphreys’ laboratory was recently pre-published in bioRxiv (pronounced “bio-archive”). The manuscript, Comparative analysis of kidney organoid and adult human kidney single cell and single nucleus transcriptomes, defines the kidney organoid cell diversity, identifies a major roadblock for current directed differentiation protocols and provides a human adult kidney snRNA-seq dataset against which to benchmark future progress.

Pre-publishing in bioRxiv is intended for the rapid sharing of new research. Authors are able to make their findings available immediately to the scientific community and can receive feedback via social media and on-site commenting on draft manuscripts before they are submitted to journals.

Launched in 2013, bioRxiv is a free, online archive and distribution service for unpublished manuscripts in biological sciences; the posted articles are referred to as preprints. Cold Spring Harbor Laboratory, a not-for-profit research and educational institution, operates the preprint server.

In 2017, CZI announced a grant to bioRxiv to fund expansion of the server and the addition of more software tools. The funding will assure that access will be made available to many more researchers – at no cost. CZI believes that increased access to the preprint will “dramatically accelerate the pace of discovery, and in turn, our understanding of health and disease”.

While physical scientists have been posting unreviewed preprints of their research for decades (see the site arXiv), the practice is now becoming popular with biologists. Approximately 800 papers were hosted at bioRxiv in 2013; in 2017, that number was over 10,000. As of July 2017, the number of submissions exceeded 1,000 per month. It was recently announced that authors who submit a manuscript to any of the PLOS journals will have their work automatically posted to bioRxiv. Each paper posted to bioRxiv is assigned a preprint DOI, so it is citable.

Dr. Humphreys is satisfied with his bioRxiv preprint experience. “Traditionally authors do not share unpublished data out of concerns of getting scooped by other laboratories. But I was pleased to receive several ideas for new experiments that would improve our paper from readers of our preprint – ideas that I had not thought of. In the end I am confident that our manuscript will be better because we uploaded it to bioRxiv before peer review.”

View and comment on Dr. Humphreys’ preprint. Authors: Haojia Wu, Kohei Uchimura, Erinn Donnelly, Yuhei Kirita, Samantha A Morris, Benjamin D Humphreys.

Follow Dr. Humphreys and Dr. Morris on Twitter.

See here for Science magazine’s discussion of preprints in biology.