
via Medical Xpress
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.
Learn more: New computational method could advance precision medicine
The Latest on: Patterns of gene expression
via Google News
The Latest on: Patterns of gene expression
- Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathologyon March 1, 2021 at 8:51 am
Tau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to ...
- Genome-wide analysis of changes in miRNA and target gene expression reveals key roles in heterosis for Chinese cabbage biomasson March 1, 2021 at 4:11 am
Comparisons of the growth and heterosis of a Chinese cabbage F 1 hybrid and its inbred parent lines. Fig. 2: Overview of differentially expressed miRNAs (DEMs) in the F 1 hybrid and the mid-parent ...
- Differing gene functions across species may pose problems for autism modelson February 22, 2021 at 4:03 am
Misaligned gene expression maps suggest that some autism-linked genes play distinct roles in mouse and human brains.
- Differences in gene expression may explain mental disorder symptomson February 15, 2021 at 9:09 am
Differences in gene expression may explain why mental illnesses with similar genetic roots can have such different symptoms, according to a new study. Genome-wide association studies (GWAS) have shown ...
- Distinctness of mental disorders traced to differences in gene readoutson February 8, 2021 at 4:46 pm
A new study suggests that differences in the expression of gene transcripts - readouts copied from DNA that help maintain and build our cells - may hold the key to understanding how mental disorders ...
- Distinctness of mental disorders traced to differences in gene readoutson February 8, 2021 at 4:00 pm
A new study suggests that differences in the expression of gene transcripts—readouts copied ... genetic risk factors result in different patterns of onset, symptoms, course of illness, and ...
- β-Catenin/Tcf7l2–dependent transcriptional regulation of GLUT1 gene expression by Zic family proteins in colon canceron February 4, 2021 at 4:00 pm
we knocked out the Zic5 gene and analyzed the chromatin localization pattern and transcriptional regulation of target gene expression. We found that Zic5 regulates glucose metabolism, and Zic5 ...
- Blood Gene Expression Signatures Predict Invasive Candidiasison February 2, 2021 at 4:00 pm
Gene expression profiling is an approach for developing early ... pathogens and also initiate and modulate the responses from adaptive immune cells via pattern recognition receptors such as Toll-like ...
- Transvection regulates the sex-biased expression of a fly X-linked geneon January 21, 2021 at 1:49 pm
Science, this issue p. 396 Sexual dimorphism in animals results from sex-biased gene expression patterns. These patterns are controlled by genetic sex determination hierarchies that establish the sex ...
- The metabolic secretome of apoptotic cells influences gene expression programs in neighboring cellson August 5, 2020 at 12:40 pm
The metabolites are shown to influence gene expression patterns in the surrounding tissue environment, in particular by restricting inflammation and promoting wound healing. A cocktail of select ...
via Bing News