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"Lück, Juliane"
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A minimal model of peptide binding predicts ensemble properties of serum antibodies
by
Bruni, Nicole
,
Greiff, Victor
,
Hartmann, Susanne
in
Algorithms
,
Amino acids
,
Animal Genetics and Genomics
2012
Background
The importance of peptide microarrays as a tool for serological diagnostics has strongly increased over the last decade. However, interpretation of the binding signals is still hampered by our limited understanding of the technology. This is in particular true for arrays probed with antibody mixtures of unknown complexity, such as sera. To gain insight into how signals depend on peptide amino acid sequences, we probed random-sequence peptide microarrays with sera of healthy and infected mice. We analyzed the resulting antibody binding profiles with regression methods and formulated a minimal model to explain our findings.
Results
Multivariate regression analysis relating peptide sequence to measured signals led to the definition of amino acid-associated weights. Although these weights do not contain information on amino acid position, they predict up to 40-50% of the binding profiles' variation. Mathematical modeling shows that this position-independent ansatz is only adequate for highly diverse random antibody mixtures which are not dominated by a few antibodies. Experimental results suggest that sera from healthy individuals correspond to that case, in contrast to sera of infected ones.
Conclusions
Our results indicate that position-independent amino acid-associated weights predict linear epitope binding of antibody mixtures only if the mixture is random, highly diverse, and contains no dominant antibodies. The discovered ensemble property is an important step towards an understanding of peptide-array serum-antibody binding profiles. It has implications for both serological diagnostics and B cell epitope mapping.
Journal Article
Mitigating effects of nonlinearities in homodyne quadrature interferometers
by
Al-Kershi, Sara
,
Sarkar, Pritam
,
Carlassara, Matteo
in
Control methods
,
Gravitational waves
,
Interferometers
2025
Homodyne Quadrature interferometers (HoQI) are an interferometric displacement sensing scheme proven to have excellent noise performance, making them a strong candidate for sensing and control schemes in gravitational wave detector seismic isolation. Like many interferometric schemes, HoQIs are prone to nonlinear effects when measuring displacements. These nonlinearities, if left unsuppressed, would substantially limit the use cases of HoQIs. This paper first shows a means of measuring and quantifying nonlinearities using a working HoQI and a mechanical resonator. We then demonstrate a method for real-time correction of these nonlinearities and several approaches for accurately calibrating the correction technique. By correcting in real time, we remove one of the biggest obstacles to including HoQIs in upgrades to future gravitational wave detectors. Finally, we discuss how to post correct data from HoQIs, suppressing even further the nonlinearity-induced errors, broadening the appeal of such sensors to other applications where measurement data can be reconstructed after the fact. We demonstrate all of this on a working HoQI system and show the measured suppression of nonlinear effects from each of these methods. Our work makes HoQIs a more broadly applicable tool for displacement sensing.