Scientific

Bioinformatics


We provide consultancy on the mathematical and computational aspects of biology. This includes consultancy on data storage, data modeling, statistical/signal analysis.

Deep Sequencing/Sequencing by Synthesis- Deep sequencing is a technique in which a DNA string is split into fragments of 200 to 300 basepairs. These fragments are then attached to a solid surface and on this surface amplified (solid state PCR). Afterward, for each of these clusters, 36 basepairs are sequenced by synthesizing the second strand. This process typically leads to around 60'000'000 short fragment reads. Here we aggregated a number of notes that might be valuable for users of an Illumina GA2 machine.
Highly Detailed Cross Correlation Analysis of Genomic Signal Tracks- This technique allows the finding of relations between multiple deep sequencing genomic signal tracks. The method finds relations between peaks/peaks, peaks/areas and areas/areas over short and/or long distances. Using this method we revisit previously published acetylation and methylation patterns and present around 1760 maps, one for each combination of histone modifications. The resulting correlation maps are browsable and reveal a variety of highly interesting colocations.
Mass Spectrometry Denoising- MALDI-TOF mass spectrometry is a well known and widely used technique to fingerprint and sequence proteins. A careful investigation of the mass spectra output from unnamed machines shows a number of artifacts produced by the machines themselves. Because these artifacts complicate a number of procedures we created a wavelet based denoising technique.
2DE Gel Correlation Analysis - Two-dimensional gel electrophoresis (2DE) is a powerful technique to examine post-translational modifications of complexly modulated proteins. Currently, spot detection is a necessary step to assess relations between spots and biological variables. This often proves time consuming and difficult when working with non-perfect gels. We developed an analysis technique to measure correlation between 2DE images and biological variables on a pixel by pixel basis. After image alignment and normalization, the biological parameters and pixel values are replaced by their specific rank. These rank adjusted images and parameters are then put into a standard linear Pearson correlation and further tested for significance and variance.
2DE Gel Denoising - when working with 2D electrophoretic gels, the photographed images often have all kinds of artifacts in them. Such gels are often regarded as 'bad' and while it may be true that they can be better, in practice the necessary information might still be present. By using specific denoising techniques it is possible to retrieve this information, thereby removing many of the unwanted effects
2DE Gel Image Registration / Overlaying - before analysis is possible, image alignment (also called registration) is often necessary. We provide techniques to overlay multiple gels, which can lead to automatic protein isoform detection.
Micro Array Analysis - To perform a quantitative analysis with gene-arrays, one must take into account inaccuracies (experimental variations, biological variations and other measurement errors) which are seldomly known. For each micro array analysis we investigated amplification and noise propagation related errors by measuring intensity dependent variations. Based on a set of control samples, we create confidence intervals on up and down regulations.
Screening Normalization - Surprisingly enough, the techniques developed for Micro-array normalization are suitable as well in the context of siRNA screening. The main difference is that instead of measuring the effect 1 siRNA has on a cell system, a reporter system will measure the effect different siRNA's has on the same reporter system.
Real Time PCR / qPCR Analysis - A calculator we developed. It takes as input the exported CT values of a Roche LightCycler and calculates the up and down-regulation of genes between two samples suing the ΔΔCT method. In short this method first calculates the normalized CT time for each sample (by subtracting the gene CT time from the reference gene CT time). Afterward these two ΔCT values are compared by subtracting the ΔCT of the altered sample from the ΔCT value from the non altered sample. The result is the log2 ratio of the up or down regulation. This value is then transformed to the actual regulation using 2^-(ΔΔCT) and reported accordingly.
Assessment of related proteins - By means of a protein interaction map we are able to deduce which proteins are very likely influenced by a specific cell system alteration. See the work done on MK5. A full description is available here
Tracking Mice on an Elevated Maze - To observe the difference in behavior between transgenic and non transgenic mice, standard behavioral tests exists. Two of these tests are the elevated maze and the light dark box. We developed a novel technique to assess the presence of each mouse throughout each test.


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