Today, tracking the development of individual cells and spotting the associated factors under the microscope is nothing unusual. However, impairments like shadows or changes in the background complicate the interpretation of data. Now, researchers at the Technical University of Munich (TUM) and the Helmholtz Zentrum München have developed a software that corrects images to make hitherto hidden development steps visible.
When stem cells develop into specialized cells, this happens in multiple steps. But which regulatory proteins are active during the decisive branching on the development path? Using so-called time-lapse microscopy, researchers can observe individual cells at very high time resolutions and, using fluorescent labelling, they can recognize precisely which of these proteins appear when in the cell.
Once a stem cell has been identified, it can be closely observed over several days using cell-tracking software. Yet, this “surveillance work” often turns out to be difficult. “The imaging data is frequently marred by irregular brightness and faded backgrounds in the time-lapse,” explains Dr. Carsten Marr, heading the workgroup Quantitative Single Cell Dynamics at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum München. “This makes it difficult or impossible to detect proteins that are decisive when a cell opts for a specific development direction, so-called transcription factors.”
Algorithms that filter out these kinds of artefacts exist, but they require either specifically prepared reference images, many images per dataset or complex manual adjustments. Furthermore, none of the existing methods correct alterations in the background over time, which hamper the quantification of individual cells.
Algorithm eliminates background changes
Now, Dr. Tingying Peng, member of Dr. Carsten Marr’s group at the Helmholtz Zentrum München and Professor Nassir Navab, head of the Chair for Computer Aided Medical Procedures and Augmented Reality at TU Munich, present an algorithm that corrects these artefacts using only a few images per dataset.
The software is called “BaSiC” and is freely available. It is compatible with many image formats commonly used in bioimaging, including mosaics pieced together from numerous smaller images and used, for example, to render large tissue regions. “Contrary to other programs, however,” explains Dr. Peng, “BaSiC can correct changes in the background of time-lapse videos. This makes it a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on.”
Bringing significant details to light
How well the new image correction program improves the analysis of individual stem cell development steps the scientists demonstrated with time-lapse videos of blood stem cells. They recorded the videos to observe cells over a six-day time span. At a certain point during this observation period undifferentiated precursor cells choose between two possible tacks of development that lead to the formation of different mature blood cells.
In images corrected using BaSiC, the researchers could identify a substantial increase in the intensity of a specific transcription factor in one of the two cell lines, while the amount of his protein in the other cell line remained unchanged. Without the image correction, the difference was not ascertainable.
“Using BaSiC, we were able to make important decision factors visible that would otherwise have been drowned out by noise,” says Nassir Navab. “The long-term goal of this research is to facilitate influencing the development of stem cells in a targeted manner, for example to cultivate new heart muscle cells for heat-attack patients. The novel possibilities for observation are bringing us a step closer to this goal.”
The BaSiC image correction program resulted from a close collaboration between the Chair of Mathematical Modeling of Biological Systems and the Chair of Computer Aided Medical Procedures & Augmented Reality at the Technical University of Munich and the Institute of Computational Biology (ICB) of the Helmholtz Zentrum München. Also involved were the Department of Biochemistry and Biophysics at the University of California in San Francisco (USA), as well as the Department of Biosystems Science and Engineering (D-BSSSE) at ETH Zürich and the Chair of Computer Aided Medical Procedure at Johns Hopkins University in Baltimore (USA).
Tingying Peng, Kurt Thorn, Timm Schroeder, Lichao Wang, Fabian J. Theis, Carsten Marr and Nassir Navab. BaSiC: A Tool for Background and Shading Correction of Optical Microscopy Images.
Nature Communications 8, 14836 (2017) – DOI: 10.1038/ncomms14836
Dr. Carsten Marr
ICB Institute of Computational Biology
Helmholtz Zentrum München
Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
Tel.: +49 89 3187 2158 – e-mail: firstname.lastname@example.org
Web: http://bit.ly/2qVMp2w – Software: http://bit.ly/2sm2WfH
Prof. Dr. Nassir Navab
Chair for Computer Aided Medical Procedures and Augmented Reality
Technical University of Munich
Boltzmannstr. 3, 85748 Garching, Germany
Tel.: 089 289 17057 – e-mail: email@example.com – web: http://campar.in.tum.de/Main/NassirNavab
https://www.tum.de/en/about-tum/news/press-releases/detail/article/33987/ Link to the press release
Dr. Ulrich Marsch | Technische Universität München
Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences