Technique could help diagnose, rectify a genetic defect with gene-editing tools such as CRISPR
Scientists have devised a new computational method that reveals genetic patterns in the massive jumble of individual cells in the body.
The discovery, published in the journal eLife, will be useful in discerning patterns of gene expression across many kinds of disease, including cancer. Scientists worked out the formulation by testing tissue taken from the testes of mice. Results in hand, they’re already applying the same analysis to biopsies taken from men with unexplained infertility.
“There have been very few studies that attempt to find the cause of any disease by comparing single-cell expression measurements from a patient to those of a healthy control. We wanted to demonstrate that we could make sense of this kind of data and pinpoint a patient’s specific defects in unexplained infertility,” said co-senior author Donald Conrad, Ph.D., associate professor and chief of the Division of Genetics in the Oregon National Primate Research Center at Oregon Health & Science University.
Simon Myers, Ph.D., of the University of Oxford, also is a senior co-author.
Conrad said he expects the new method will advance the field of precision medicine, where individualized treatment can be applied to the specific nuance of each patient’s genetic readout.
The scientists made the breakthrough by applying a method recently developed at the University of Oxford to gene expression data from the massive trove of individual cells comprising even minuscule tissue biopsies. The method is known as sparse decomposition of arrays, or SDA.
“Rather than clustering groups of cells, SDA identifies components comprising groups of genes that co-vary in expression,” the authors write.
The new study applied the method to 57,600 individual cells taken from the testes of five lines of mice: Four that carry known genetic mutations causing defects in sperm production and one with no sign of genetic infertility. Researchers wanted to see whether it was possible to sort this massive dataset based on the variation in physiological traits resulting from differences in the genes expressed in the RNA, or ribonucleic acid, of individual cells.
Researchers found they were able to cut through the statistical noise and sort many thousands of cells into 46 genetic groups.
“It’s a data-reduction method that allows us to identify sets of genes whose activity goes up and down over subsets of cells,” Conrad said. “What we’re really doing is building a dictionary that describes how genes change at a single-cell level.”
The work will immediately apply to male infertility.
Infertility affects an estimated 0.5% to 1% of the male population worldwide. Current measures to treat male infertility involve focus on managing defects in the sperm itself, including through in vitro fertilization. However, those techniques don’t work in all cases.
“We’re talking about the problem where you don’t make sperm to begin with,” Conrad said.
This new technique could open new opportunities to diagnose a specific genetic defect and then potentially rectify it with new gene-editing tools such as CRISPR. Identification of a specific cause would be a vast improvement over the current state of the art in diagnosing male infertility, which amounts to a descriptive analysis of testicular tissue biopsies.
“The opportunity provided by CRISPR, coupled to this kind of diagnosis, is really a match made in heaven,” Conrad said.
The Latest on: Patterns of gene expression
via Google News
The Latest on: Patterns of gene expression
- High-throughput identification of protein functional similarities using a gene-expression-based siRNA screenon January 21, 2020 at 3:26 am
For each protein depletion, the gene expression of eight genes was quantified using the multiplexed Affymetrix Quantigene 2.0 assay in technical triplicate. As a proof of concept, six genes (BNIP3, ...
- Epigenetic Ratchet: Spontaneous Adaptation via Stochastic Gene Expressionon January 16, 2020 at 2:34 am
it is also reported that bacteria can modify their gene expression patterns to survive a huge variety of environmental conditions even without such pre-designed networks to adapt specically to each ...
- Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarrayon December 29, 2019 at 9:55 am
M. Schena and R. W. Davis, Department of Biochemistry, Beckman Center, Stanford University Medical Center, Stanford, CA 94305, USA. D. Shalon and P. O. Brown ...
- Gene Regulation & Expressionon December 22, 2019 at 4:00 pm
It also includes searching for mutated genes that confer a unique vulnerability to cancer cells and studying gene expression patterns that are associated with mutation status across all tumor types. A ...
- GENOMICS START-UP TARGETS GENE EXPRESSION PATTERNS PECULIAR TO CELLon November 28, 2019 at 7:10 am
Roseville, Calif.-based US Kidney Research Corp., formerly Curion Research Corp., has been working on its waterless renal replacement technology since its ...
- Spatial Gene Expression Profiling of Neurological Disorderson October 7, 2019 at 4:59 am
In this interview, Cedric Uytingco discusses the key benefits of being able to visualize gene expression patterns in neurological samples. Traditionally, neuroscientists used histology to infer cell ...
- What is the pattern of information flow for gene expression?on September 7, 2019 at 3:04 pm
Gene expression occurs in all cells because all cells need proteins for both structure and function. The pattern of information flow for gene expression is from DNA to RNA to protein through the ...
- GEsture: an online hand-drawing tool for gene expression pattern searchon June 20, 2018 at 1:31 am
Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene ...
- The effect of night shifts: gene expression fails to adapt to new sleep patternson May 7, 2018 at 5:00 pm
A team of researchers from the McGill University affiliated Douglas Mental Health University Institute (DMHUI) has discovered that genes regulating important biological processes are incapable of ...
- Changes in gene activity may one day reveal the time of death for crime victimson February 13, 2018 at 8:33 am
The more genes analyzed, the more expensive the work, Tagkopoulos says. Even so, Guigó is eager to see what else he can learn from these patterns. “Changes in gene expression may also carry the ...
via Bing News