Computational tool translates complex data into simplified 2-dimensional images

May 19, 2013, Columbia University Medical Center
viSNE reveals the progression of cancer in a sample of cells taken from a patient with acute myeloid leukemia. In figure a, the contours represent cell density in each region of the map. Each point represents a cell from the diagnosis sample (top, purple) or relapse sample (bottom, red). In figure b, cells from both diagnosis and relapse samples are shown in each map. Cells are colored according to intensity of expression of the indicated cell markers, enabling the comparison of expression patterns before and after relapse. For example, Fit3 is expressed primarily in the diagnosis sample, while CD34 emerges in the relapse sample. Credit: Dana Pe'er, PhD/Columbia University

In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual cells. These technologies have led to new challenges, however, as scientists now struggle with how to make sense of the resulting trove of data. Now a solution may be at hand. Researchers at Columbia University and Stanford University have developed a computational method that enables scientists to visualize and interpret "high-dimensional" data produced by single-cell measurement technologies such as mass cytometry. The method, published in the online edition of Nature Biotechnology, has particular relevance to cancer research and therapeutics.

Researchers now understand that cancer within an individual can harbor subpopulations of cells with different . Groups of cells may behave differently from one another, including in how they respond to treatment. The ability to study single cells, as well as to identify and characterize subpopulations of within an individual, could lead to more precise methods of diagnosis and treatment.

"Our method not only will allow scientists to explore the of cancer cells and to characterize drug-, but also will allow physicians to track , identify drug-resistant cancer cells, and detect minute quantities of cancer cells that increase the risk of relapse," said co-senior author Dana Pe'er, PhD, associate professor of biological sciences and at Columbia. The other co-senior author is Garry P. Nolan, PhD, professor of microbiology & immunology at Stanford.

The method, called viSNE (visual interactive Stochastic Neighbor Embedding), is based on a sophisticated algorithm that translates high-dimensional data (e.g., a dataset that includes many different simultaneous measurements from single cells) into visual representations similar to two-dimensional "scatter plots"—the simple graphs with X and Y axes that many people first encounter in high school math and biology. "Basically, viSNE provides a way to visualize very high-dimensional data in two dimensions, while maintaining the most important organization and structure of the data," said Dr. Pe'er. "Color is used as a third dimension to enable users to interactively visualize various features of the cells."

The viSNE software can analyze measurements of dozens of molecular markers. In the two-dimensional maps that result, the distance between points represents the degree of similarity between single cells. The maps can reveal clearly defined groups of cells with distinct behaviors (e.g., drug resistance) even if they are only a tiny fraction of the total population. This should enable the design of ways to physically isolate and study these cell subpopulations in the laboratory.

Although the algorithm underlying the method is complex, Dr. Pe'er expects that all researchers, no matter their level of mathematical expertise, will be able to use viSNE.

To demonstrate the software's utility, Dr. Pe'er and her colleagues used mass cytometry and viSNE to study bone marrow cells from patients with acute myeloid leukemia. Currently, clinicians can incorporate at most 4 to 8 markers to assess the cells. Because mass cytometry and viSNE can incorporate many more markers, viSNE is able to identify more subtle differences between cells. Using the algorithm, Dr. Pe'er and her colleagues were able to reveal previously unrecognized heterogeneity in the bone marrow cells they studied.

The researchers also showed that viSNE could detect minimal residual disease (MRD)—extremely small quantities of cancer cells that persist after chemotherapy and raise the risk of recurrence. "In blinded tests, we were able to find as few as 20 out of tens of thousands of healthy cells," said Dr. Pe'er. Such a small quantity of cells is extremely difficult to detect, even by the most experienced pathologist.

"The ability to detect MRD is critical for curing cancer," added Dr. Pe'er. "Eliminating even 99.9 percent of a tumor doesn't bring about a cure. You have to be able to find, and then eliminate, the tiny populations of that can survive therapy and lead to disease relapse."

Explore further: Breast cancer researchers find new drug target companion prognostic test for hormone therapy resistance

Related Stories

Breast cancer researchers find new drug target companion prognostic test for hormone therapy resistance

April 1, 2013
A team of international cancer researchers led by Dr. Mathieu Lupien at the Princess Margaret Cancer Centre, University Health Network, has identified the signalling pathway that is over-activated in estrogen receptor (ER)-positive ...

Heterogeneous ER+ breast cancer models allow more accurate drug testing

August 6, 2012
(Medical Xpress) -- Cell cultures are homogeneous. Human tumors are not. A University of Colorado Cancer Center study recently published in the journal Breast Cancer Research and Treatment reports the development of human-derived ...

Key bone marrow protein identified as potential new leukemia treatment target

April 15, 2013
A new study on how the progression of acute lymphocytic leukemia (ALL) is influenced by the bone marrow environment has demonstrated for the first time that targeting a specialized protein known as osteopontin (OPN) may be ...

Computer program identifies rare mutations harbored within diverse populations of cancer cells and microorganisms

April 24, 2013
A tumor is not a uniform mass of identical cells. However, teasing apart genetic heterogeneity within a biopsied tumor can be difficult. Researchers often fail to tell the difference between a rare variant in a DNA dataset ...

Signature of circulating breast tumor cells that spread to the brain found

April 10, 2013
Some breast tumor circulating cells in the bloodstream are marked by a constellation of biomarkers that identify them as those destined to seed the brain with a deadly spread of cancer, said researchers led by those at Baylor ...

Scientists seek out cancer cells hiding from treatment

January 15, 2013
Scientists hope to improve leukaemia treatment by investigating how cancer cells use 'hiding places' in the body to avoid chemotherapy drugs.

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.