Navigation Links
Whitehead scientists identify major flaw in standard approach to global gene expression analysis

CAMBRIDGE, Mass. (October 25, 2012) Whitehead Institute researchers report that common assumptions employed in the generation and interpretation of data from global gene expression analyses can lead to seriously flawed conclusions about gene activity and cell behavior in a wide range of current biological research.

"Expression analysis is one of the most commonly used methods in modern biology," says Whitehead Member Richard Young. "So we are concerned that flawed assumptions may affect the interpretation of many biological studies."

Much of today's interpretation of gene expression data relies on the assumption that all cells being analyzed have similar total amounts of messenger RNA (mRNA), the roughly 10% of a cell's RNA that acts as a blueprint for protein synthesis. However, some cells, including aggressive cancer cells, produce several times more mRNA than other cells. Traditional global gene expression analyses have typically ignored such differences.

"We've highlighted this common assumption in gene expression analysis that potentially affects many researchers," says Tony Lee, a scientist in Young's lab and a corresponding author of the article published in this week's issue of Cell. "We provided a concrete example of the problem and a solution that can be implemented by investigators."

Members of the Young lab recently uncovered the flaw while investigating genes expressed in cancer cells expressing high levels of c-Myc, a gene regulator known to be highly expressed in aggressive cancer cells. When comparing cells with high and low c-Myc levels, they were surprised to find very different results using different approaches to gene expression analysis. Further investigation revealed that there were striking differences in the total amounts of RNA from the high and low c-Myc -containing cells, yet these differences were masked by commonly used experimental and analytical methods.

"The different results we saw from different methods of gene expression analysis were shocking, and led us to reinvestigate the whole process on several platforms," says Jakob Lovn, postdoctoral reseacher in Young's lab and co-author of the Cell paper. "We then realized that the common assumption that cells contain similar levels of mRNA is badly flawed and can lead to serious misinterpretations, particularly with cancer cells that can have very different amounts of RNA."

In addition to delineating this problem, the Whitehead scientists also describe a remedy. By using synthetically produced mRNAs, called RNA spike-ins, as standardized controls, researchers can compare experimental data and eliminate assumptions about total cell RNA amounts. The remedy applies to all three gene expression analysis platforms they studied.

Although the researchers believe the use of RNA spike-ins should become the new standard for global gene expression analyses, questions are likely to persist about the interpretations of much prior research.

"There are over 750,000 expression datasets in public databases, and because they generally lack information about the cell numbers used in the analysis, it is unclear whether they can be re-examined in order to validate the original interpretation" says David Orlando, a scientist in the Young lab. "It may be necessary to reinvestigate some important concepts."

Contact: Nicole Rura
Whitehead Institute for Biomedical Research

Related biology news :

1. USDA scientists collaborate with global researchers to advance the mapping of the barley genome
2. Scientists uncover mechanism by which plants inherit epigenetic modifications
3. CT scan and 3-D print help scientists reconstruct an ancient mollusk
4. Scientists conclude high fructose corn syrup should not be blamed for obesity
5. Maintaining Earths sustainability: Scientists, engineers, educators take coordinated approach
6. UMN scientists get federal grant for biotechnology development to purify fracking water
7. Scientists reveal how natural antibiotic kills tuberculosis bacterium
8. Chinese scientists discover MVK mutations associated with DSAP
9. Oil from algae closer to reality through studies by unique collaboration of scientists
10. A rare feat: 2 scientists at Salk score NIH New Innovator Awards
11. Scientists discover how the brain ages
Post Your Comments:
(Date:6/20/2016)... , June 20, 2016 Securus Technologies, ... technology solutions for public safety, investigation, corrections and ... prisons involved, it has secured the final acceptance ... facilities for Managed Access Systems (MAS) installed. Furthermore, ... facilities to be installed by October, 2016. MAS ...
(Date:6/15/2016)... , June 15, 2016 ... report titled "Gesture Recognition Market by Application Market - Global Industry ... - 2024". According to the report, the  global gesture ... in 2015 and is estimated to grow at ... billion by 2024.  Increasing application of ...
(Date:6/9/2016)... June 9, 2016 Paris ... Teleste,s video security solution to ensure the safety of people ... during the major tournament Teleste, an international ... and services, announced today that its video security solution will ... to back up public safety across the country. The system ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016  Blueprint Bio, a company dedicated to ... medical community, has closed its Series A funding round, ... "We have received a commitment from Forentis ... need to meet our current goals," stated Matthew ... runway to complete validation on the current projects in ...
(Date:6/23/2016)... ... 23, 2016 , ... ClinCapture, the only free validated electronic ... showcase its product’s latest features from June 26 to June 30, 2016 for ... Disrupting Clinical Trials in The Cloud during the conference. DIA (Drug Information ...
(Date:6/23/2016)... FRANCISCO , June 22, 2016  Amgen (NASDAQ: ... sponsorship of the QB3@953 life sciences incubator ... human health. The shared laboratory space at QB3@953 was ... overcome a key obstacle for many early stage organizations ... part of the sponsorship, Amgen launched two "Amgen Golden ...
(Date:6/22/2016)... 2016 Research and Markets has announced the ... to their offering. The ... $29.3 billion in 2013. The market is expected to grow at ... to 2020, increasing from $50.6 billion in 2015 to $96.6 billion ... the forecast period (2015 to 2020) are discussed. As well, new ...
Breaking Biology Technology: