Computer Analysis Completes Antibody Blueprint
Antibodies defend our bodies against intruders. These molecules consist of proteins with attached sugars. However, the blueprint directing the processing of these sugars on the protein was not well understood until now. In a paper published in the journal Nature Communications, scientists from the Helmholtz Zentrum München used computer analysis to complete this blueprint and confirmed their findings in the laboratory.
The authors specifically studied IgG antibodies.* These are the most common antibodies in blood and act especially against viruses and bacteria. "They have a characteristic Y shape and are composed mainly of protein", explains Elisa Benedetti, PhD student at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum München. "However, during their production, the cell attaches different sugars to these protein molecules, and how this happens was until now not well understood", continues the first author of the study.
Understanding this process is of great interest to researchers, because the identity of the sugar that is attached (in a process called glycosylation) dramatically influences the function of the antibody. While one sugar molecule might promote inflammation upon contact with an antigen, another might suppress the immune response.
Using computers to solve a biochemical problem
"The difficulty in studying the glycosylation blueprint lies, among other things, in the complex regulation of how the corresponding enzymes work", explains last author Dr. Jan Krumsiek, junior group leader at the ICB and Junior Fellow at the Technical University of Munich. The bioinformaticians' strategy to solve this biochemically difficult problem was to tackle it in the digital realm.
To this end, the scientists analyzed data from the Croatian '10001 Dalmatians Biobank'. They first studied blood samples from almost 700 test subjects aged between 18 und 88 with respect to the sugars attached to their IgG antibodies. By investigating the correlation of the measured glycans to each other, authors found that they largely corresponded to previous known steps in the enzymatic process of IgG glycosylation. Indeed, on the basis of the data, the algorithm could reconstitute the already known blueprint - and develop it further.
"We could predict new steps of how the sugar residues must be attached to the antibodies", explains Krumsiek. "Using three additional cohorts comprising over 2,500 samples, we were able to replicate the statistical data." Subsequently, the researchers could substantiate the predicted steps using further methods: firstly, on the basis of a genome-wide association study with about 1,900 samples from the Augsburg-based KORA research platform**, and, additionally, in a series of three experiments in the laboratory.
"We could show in vitro that at least one of our predicted reactions is enzymatically feasible and we demonstrated in cell culture that particular enzymes that are predicted to work together in the model, do actually co-localize in the cell, that is, they are spatially very close to each other", says Krumsiek. "Our study shows how information technology and classical bench chemistry can support and enhance each other."
This article has been republished from materials provided by Helmholtz Zentrum München. Note: material may have been edited for length and content. For further information, please contact the cited source.
The Genes That Make Quorn a Fungal Food FavoriteNews
The meat substitute Quorn is derived from a fungus called Fusarium venenatum. A very similar fungus, F. graminearum, is one of the world's most damaging crop diseases. A new genome study shows why one fungus makes food, and the other destroys it.READ MORE
Neural Computer Hears Like HumansNews
Modelling the human senses is an incredibly complex task. Our brains arrange cells into complex hierarchies that process information from our surroundings. Now, a group at MIT have created a model of the human auditory cortex that can hear sounds and music in the same way that humans do.READ MORE
Stable Beta-Amyloid Dimers Identified in Alzheimer’s BrainsNews
A recent study exploited state-of-the-art mass spectrometry to provide the first direct evidence of beta-amyloid dimers in patients with Alzheimer’s disease and points to the potential of these molecules as biomarkers. Beta-amyloid dimers may be the smallest pathological species that trigger Alzheimer’s disease.
Comments | 0 ADD COMMENT
International Conference on Analytical and Bio Analytical Techniques
Oct 31 - Nov 01, 2018