Cell publishes the functional pattern of basic genes! The function of more than 5,000 genes needed for human cells to survive

Using a novel, ensemble, image-based screening method, a team of scientists at the Whitehead Institute, the Massachusetts Institute of Technology and Harvard University's Broad Institute systematically assessed the function of
more than 5,000 basic human genes.
Their analysis, which leverages CRISPR/Cas9 knockout gene activity, forms an unprecedented resource to understand and visualize a wide range of gene functions
in cellular processes through spatial and temporal resolution.
The team's findings, published in the journal Cell, cover more than 31 million individual cells and include quantitative data on hundreds of different parameters, making it possible to
predict how genes work and work together.

"Throughout my career, I've wondered what happens to cells when the function of an important gene is eliminated," said
Iain Cheeseman of the Whitehead Institute, senior author of the study.
"Now, we can do this, not just for one gene, but for every gene involved in the division of human cells in a dish, which is very powerful
.
" The resources we create will benefit not only our own labs, but labs around the world
.
”

Essential genes control the basic functions needed for cell survival (transcription, mRNA splicing, translation, vesicle trafficking, DNA replication, cell division, etc.
).

Systematically disrupting the function of these genes is not a new concept, but traditional methods are limited by a variety of factors, including cost, feasibility, and the ability to completely eliminate the
activity of essential genes.

Cheeseman and his colleagues worked with other teams to identify and achieve this ambitious common goal
.
Broad researchers have pioneered a new genetic screening technique that combines two approaches: large-scale, ensemble genetic screening using CRISPR/Cas9, and imaging cells to reveal quantitative and qualitative differences
.
In addition, this method is inexpensive compared to other methods and is
practiced using commercially available devices.

Blainey said: "We are proud to demonstrate the incredible resolution of cellular processes, a low-cost imaging analysis
in collaboration with the Iain Laboratory at the Whitehead Institute.
Obviously, this is just the tip
of the iceberg of our approach.
The ability to link genetic perturbations based on more detailed phenotypic readings is urgently needed and can now be advanced
in many areas of research.
”

Cheeseman added: "The ability to combine cell bioscreening is a fundamental game-changer
.
You have two adjacent cells, so your ability to make statistically significant calculations on whether they are the same is much higher, and you can discern very small differences
.
”

Cheeseman, Blainey, lead authors Luke Funk and Kuan-Chung Su and their colleagues evaluated the function of
5,072 basic genes in human cell lines.
They analyzed four markers of the cells on the screen: DNA; DNA damage response, a key cellular pathway that detects and responds to damaged DNA; There are also two important structural proteins, actin and tubulin
.
In addition to the initial screening, the scientists conducted a small-scale follow-up screening
of about 200 genes involved in cell division, also known as "mitosis.
" These genes were identified in the initial screening to play a definite role in mitosis, but they had not previously been found to be associated with
the mitotic process.
The data, available through a companion website called Vesuvius, provides a resource
for other scientists to study the function of the genes they are interested in.

"We collected a lot of information
from these cells.
For example, for the nucleus, it is necessary not only to see how bright its staining is, but also to see how big and round it is, and whether the edges are smooth or uneven?" Computers can really extract a lot of spatial information
.
”

From this rich multidimensional data, the scientists' work provides a cell-biological "fingerprint"
for each gene analyzed on the screen.
Using sophisticated computational clustering strategies, researchers can compare these fingerprints to each other and construct potential regulatory relationships
between genes.
Because the team's data confirm multiple known relationships, it can be used to make confident predictions
about genes whose function and/or interaction with other genes are unknown.

The researchers' screening data yielded a number of notable findings, including a startling discovery
related to ion channels.
The two genes, AQP7 and ATP1A1, play a role in mitosis, especially in
the proper separation of chromosomes.
These genes encode membrane-binding proteins that transport ions in and out of cells
.
"In all the years I've been studying mitosis, I never thought ion channels would be involved," Cheeseman said
.

He added: "We're really just scratching the surface
out of our data.
We hope that many others will not only benefit from this resource, but build on it
.
”

This work was supported
by the National Institutes of Health, the Gordon and Betty Moore Foundation, the Defense Science and Engineering Graduate Fellowship, and the Natural Sciences and Engineering Research Council Fellowship.

Original:

The phenotypic landscape of essential human genes