Human gene-function map available to all scientists

Every single human gene has been linked to its function by scientists from the Massachusetts Institute of Technology, who have made the comprehensive gene-function map freely available to the scientific community.

The completion of the Human Genome Project gave scientists access to the sequence of every human gene (see BioNews 1098 and 1140). Now, graduate students Joseph Replogle and Reuben Saunders leveraged recently developed molecular tools to assign a specific function to each gene. They also exploited their new database to answer questions about mitochondrial gene regulation, aneuploidy, and the function of the orphan gene C7orf26.

'It's a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research,' said senior study lead Professor Jonathan Weissman. 'Rather than defining ahead of time what biology you're going to be looking at, you have this map of the genotype-phenotype relationships and you can go in and screen the database without having to do any experiments.'

Perturb-seq is the technology behind this achievement and was developed in 2016 by Professor Weissman and collaborator Professor Aviv Regev. It uses CRISPR/Cas9 genome editing to introduce genetic changes into selected cells, combining this with single cell RNA sequencing to determine which RNAs are expressed as a consequence of the genetic change.

Initially, the approach was costly and limited to small data sets. Saunders and Replogle used computational and high-throughput technologies to up-scale the method and applied it to the entire human genome, analysing over 2.5 million cells.

Assessing the function of individual genes at the level of the single cell is a distinct feature of Perturb-seq and sets it apart from traditional genetic analysis: 'We often take all the cells where "gene X" is knocked down and average them together to look at how they changed,' explained Professor Weissman. 'But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behaviour may be missed by the average.'

The current study, which was published in Cell, used two different cell lines, one derived from human blood cancer cells, the other one from the retina. In the future, other cell types could be investigated in the same way to describe the cell-specific function of genes with even more detail.