(Press-News.org) HOUSTON — In an effort to address a major challenge when analyzing large single-cell RNA-sequencing datasets, researchers from The University of Texas MD Anderson Cancer Center have developed a new computational technique to accurately differentiate between data from cancer cells and the variety of normal cells found within tumor samples. The work was published today in Nature Biotechnology.
The new tool, dubbed CopyKAT (copy number karyotyping of aneuploid tumors), allows researchers to more easily examine the complex data obtained from large single-cell RNA-sequencing experiments, which deliver gene expression data from many thousands of individual cells.
CopyKAT uses that gene expression data to look for aneuploidy, or the presence of abnormal chromosome numbers, which is common in most cancers, said study senior author Nicholas Navin, Ph.D., associate professor of Genetics and Bioinformatics & Computational Biology. The tool also helps to identify distinct subpopulations, or clones, within the cancer cells.
"We developed CopyKAT as a tool to infer genetic information from the transcriptome data. By applying this tool to several datasets, we showed that we could unambiguously identify, with about 99% accuracy, tumor cells versus the other immune or stromal cells present in a mixed tumor sample," Navin said. "We could then go one step further to discover the subclones present and understand their genetic differences."
Historically, tumors have been studied as a mixture of all cells present, many of which are not cancerous. The advent of single-cell RNA sequencing in recent years has enabled researchers to analyze tumors in much greater resolution, examining the gene expression of each individual cell to develop a picture of the tumor landscape, including the surrounding microenvironment.
However, it's not easy to distinguish between cancer cells and normal cells without a reliable computational approach, Navin explained. Former postdoctoral fellow Ruli Gao, Ph.D., now assistant professor of Cardiovascular Sciences at Houston Methodist Research Institute, developed the CopyKAT algorithms, which improve upon older techniques by increasing accuracy and adjusting for the newest generation of single-cell RNA-sequencing data.
The team first benchmarked its tool by comparing results to whole-genome sequencing data, which showed high accuracy in predicting copy number changes. In three additional datasets from pancreatic cancer, triple-negative breast cancer and anaplastic thyroid cancer, the researchers showed that CopyKAT was accurate in distinguishing between tumor cells and normal cells in mixed samples.
These analyses were made possible through collaborations with Stephen Y. Lai, M.D., Ph.D., professor of Head and Neck Surgery, as well as Stacy Moulder, M.D., professor of Breast Medical Oncology, and the Breast Cancer Moon Shot®, part of MD Anderson's Moon Shots Program®, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients' lives.
In analyzing these samples, the researchers also showed the tool is effective in identifying subpopulations of cancer cells within the tumor based on copy number differences, as confirmed by experiments in triple-negative breast cancers.
"By using CopyKAT, we were able to identify rare subpopulations within triple-negative breast cancers that have unique genetic alterations not widely reported, including those with potential therapeutic implications," Gao said. "We hope this tool will be useful to the research community to make the most of their single-cell RNA-sequencing data and to drive new discoveries in cancer."
The tool is freely available to researchers here. The authors note that the tool is not applicable to the study of all cancer types. Aneuploidy, for example, is relatively rare in pediatric and hematologic cancers.
INFORMATION:
This work was supported by the American Cancer Society, the National Institutes of Health/National Cancer Institute (RO1CA240526, RO1CA236864, CA016672), the Cancer Prevention & Research Institute of Texas (CPRIT) Single Cell Genomics Core Facilities Grant (RP180684), the American Association for the Advancement of Science (AAAS) Martin and Rose Wachtel Cancer Research Award, the Andrew Sabin Family Fellowship, the Jack and Beverly Randall Prize for Excellence in Cancer Research, Susan G. Komen, the Anaplastic Thyroid Cancer Patrick Research Fund and an MD Anderson research program grant.
Additional MD Anderson collaborators include: Shanshan Bai, of Genetics and Genitourinary Medical Oncology; Ying C. Henderson, M.D., Ph.D., and Jennifer Rui Wang, M.D., of Head and Neck Surgery; Yiyun Lin, Aislyn Schalck, Yun Yan, Tapsi Kumar, and Alexander Davis, Ph.D., all of Genetics and the UTHealth Graduate School of Biomedical Sciences; Min Hu, and Emi Sei, Ph.D., both of Genetics; Fang Wang, Ph.D., and Ken Chen, Ph.D., both of Bioinformatics and Computational Biology; Simona F. Shaitelman, M.D., of Radiation Oncology. The authors declare no competing interests.
Mount Sinai researchers have published one of the first studies using a machine learning technique called "federated learning" to examine electronic health records to better predict how COVID-19 patients will progress. The study was published in the Journal of Medical Internet Research - Medical Informatics on January 18.
The researchers said the emerging technique holds promise to create more robust machine learning models that extend beyond a single health system without compromising patient privacy. These models, in turn, can help triage patients and improve the quality of their care.
Federated ...
A research team from the Institut national de la recherche scientifique (INRS) has developed a process for the electrolytic treatment of wastewater that degrades microplastics at the source. The results of this research have been published in the Environmental Pollution journal.
Wastewater can carry high concentrations of microplastics into the environment. These small particles of less than 5 mm can come from our clothes, usually as microfibers. Professor Patrick Drogui, who led the study, points out there are currently no established degradation methods to handle this contaminant during wastewater ...
Philadelphia, January 18, 2021 - A new study comparing the incidence of sudden deaths occurring outside the hospital across New York City's highly diverse neighborhoods with the percentage of positive SARS-CoV-19 tests found that increased sudden deaths during the pandemic correlate to the extent of virus infection in a neighborhood. The analysis appears in Heart Rhythm, the official journal of the Heart Rhythm Society, the Cardiac Electrophysiology Society, and the Pediatric & Congenital Electrophysiology Society, published by Elsevier.
"Our research shows the highly diverse regional distribution of out-of-hospital sudden death during ...
ANN ARBOR, Mich. -- An estimated one in five teenagers has symptoms of a mental health disorder such as depression or anxiety, and suicide is the second leading cause of death among teens.
But the first person a teen confides in may not always be an adult - they may prefer to talk to another teen.
And three-quarters of parents in a new national poll think peers better understand teen challenges, compared to teachers or counselors in the school. The majority also agree that peer support leaders at school would encourage more teens to talk with someone about their mental health problems, according to the C.S. Mott Children's Hospital National Poll on Children's Health at Michigan Medicine.
"Peers may provide valuable support for ...
New research examining more than 800,000 traffic stops in Vermont over the course of five years substantiates the term "driving while Black and Brown."
Compared to white drivers, Black and Latinx drivers in Vermont are more likely to be stopped, ticketed, arrested, and searched. But they are less likely to be found with contraband than white drivers. The report finds evidence not only of racial disparities but also racial bias in policing. What's more, a number of these gaps widened over the years examined in the report. With such comprehensive data encompassing the state of Vermont, the authors also found that Vermont police stop cars at a rate ...
A student infected with COVID-19 returning home from university for Christmas would, on average, have infected just less than one other household member with the virus, according to a new model devised by mathematicians at Cardiff University and published in END ...
Variation in consumption of market-acquired foods outside of the traditional diet -- but not in total calories burned daily -- is reliably related to indigenous Amazonian children's body fat, according to a Baylor University study that offers insight into the global obesity epidemic.
"The importance of a poor diet versus low energy expenditure on the development of childhood obesity remains unclear," said Samuel Urlacher, Ph.D., assistant professor of anthropology at Baylor University, CIFAR Azrieli Global Scholar and lead author of the study. "Using gold-standard measures of energy expenditure, we show that relatively lean, rural forager-horticulturalist children in the Amazon spend approximately the same total number of calories each day as their much ...
Spiritualist mediums might be more prone to immersive mental activities and unusual auditory experiences early in life, according to new research.
This might explain why some people and not others eventually adopt spiritualist beliefs and engage in the practice of 'hearing the dead', the study led by Durham University found.
Mediums who "hear" spirits are said to be experiencing clairaudient communications, rather than clairvoyant ("seeing") or clairsentient ("feeling" or "sensing") communications.
The researchers conducted a survey of 65 clairaudient spiritualist mediums from the Spiritualists' National Union and 143 members of the general population in the ...
Tokyo, Japan - Researchers from Tokyo Metropolitan University have discovered that fruit flies with genetic modifications to enhance glucose uptake have significantly longer lifespans. Looking at the brain cells of aging flies, they found that better glucose uptake compensates for age-related deterioration in motor functions, and led to longer life. The effect was more pronounced when coupled with dietary restrictions. This suggests healthier eating plus improved glucose uptake in the brain might lead to enhanced lifespans.
The brain is a particularly power-hungry part of our bodies, consuming 20% of the oxygen we take in and 25% of the glucose. That's why it's so important that it can stay powered, ...
The spread of COVID-19 in Brazil overwhelmed the health systems in all the country's regions, particularly in areas where they were already fragile, according to a collaborative effort involving the Barcelona Institute for Global Health (ISGlobal), an institution supported by the "la Caixa" Foundation, the University of Sao Paulo, the Catholic University of Rio de Janeiro, the D'Or Institute of Research and Education and the Oswaldo Cruz Foundation. The findings, published in The Lancet Respiratory Medicine, reveal that a large percentage of COVID-19 patients that were hospitalised in Brazil required intensive care and respiratory support, and many did not survive.
The COVID-19 pandemic has put an enormous strain on healthcare ...
