MALDI-TOF Baseline Drift Removal Using Stochastic Bernstein Approximation

Stochastic Bernstein (SB) approximation can tackle the problem of baseline drift correction of instrumentation data. This is demonstrated for spectral data: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) data. Two SB schemes for removing the baseline drift are presented: iterative and direct. Following an explanation of the origin of the MALDI-TOF baseline drift that sheds light on the inherent difficulty of its removal by chemical means, SB baseline drift removal is illustrated for both proteomics and genomics MALDI-TOF data sets. SB is an elegant signal processing method to obtain a numerically straightforward baseline shift removal method as it includes a free parameter sigma(x) that can be optimized for different baseline drift removal applications. Therefore, research that determines putative biomarkers from the spectral data might benefit from a sensitivity analysis to the underlying spectral measurement that is made possible by varying the SB free parameter. This can be manually tuned ( for constant sigma) or tuned with evolutionary computation ( for sigma( x)). Copyright (C) 2006 Hindawi Publishing Corporation. All rights reserved

Development of a complete advanced computational workflow for high-resolution LDI-MS metabolomics imaging data processing and visualization

La imatge per espectrometria de masses (MSI) mapeja la distribució espacial de les molècules en una mostra. Això permet extreure informació Metabolòmica espacialment corralada d'una secció de teixit. MSI no s'usa àmpliament en la metabolòmica espacial a causa de diverses limitacions relacionades amb les matrius MALDI, incloent la generació d'ions que interfereixen en el rang de masses més baix i la difusió lateral dels compostos. Hem desenvolupat un flux de treball que millora l'adquisició de metabòlits en un instrument MALDI utilitzant un "sputtering" per dipositar una nano-capa d'Au directament sobre el teixit. Això minimitza la interferència dels senyals del "background" alhora que permet resolucions espacials molt altes. S'ha desenvolupat un paquet R per a la visualització d'imatges i processament de les dades MSI, tot això mitjançant una implementació optimitzada per a la gestió de la memòria i la programació concurrent. A més, el programari desenvolupat inclou també un algoritme per a l'alineament de masses que millora la precisió de massa.La imagen por espectrometría de masas (MSI) mapea la distribución espacial de las moléculas en una muestra. Esto permite extraer información metabolòmica espacialmente corralada de una sección de tejido. MSI no se usa ampliamente en la metabolòmica espacial debido a varias limitaciones relacionadas con las matrices MALDI, incluyendo la generación de iones que interfieren en el rango de masas más bajo y la difusión lateral de los compuestos. Hemos desarrollado un flujo de trabajo que mejora la adquisición de metabolitos en un instrumento MALDI utilizando un “sputtering” para depositar una nano-capa de Au directamente sobre el tejido. Esto minimiza la interferencia de las señales del “background” a la vez que permite resoluciones espaciales muy altas. Se ha desarrollado un paquete R para la visualización de imágenes y procesado de los datos MSI, todo ello mediante una implementación optimizada para la gestión de la memoria y la programación concurrente. Además, el software desarrollado incluye también un algoritmo para el alineamiento de masas que mejora la precisión de masa.Mass spectrometry imaging (MSI) maps the spatial distributions of molecules in a sample. This allows extracting spatially-correlated metabolomics information from tissue sections. MSI is not widely used in spatial metabolomics due to several limitations related with MALDI matrices, including the generation of interfering ions and in the low mass range and the lateral compound delocalization. We developed a workflow to improve the acquisition of metabolites using a MALDI instrument. We sputter an Au nano-layer directly onto the tissue section enabling the acquisition of metabolites with minimal interference of background signals and ultra-high spatial resolution. We developed an R package for image visualization and MSI data processing, which is optimized to manage datasets larger than computer’s memory using a mutli-threaded implementation. Moreover, our software includes a label-free mass alignment algorithm for mass accuracy enhancement

Applications of ion mobility spectrometry, collision-induced dissociation and electron activated dissociation tandem mass spectrometry to structural analysis of proteins, glycoproteins and glycans

This dissertation mainly focuses on analytical method development for characterization of proteins, glycoproteins and glycans using the recently developed ion mobility spectrometry (IMS) techniques and various electron activated dissociation (ExD) tandem mass spectrometry methods. IMS and ExD have become important techniques in structure analysis of biomolecules. IMS is a gas-phase separation method orthogonal to liquid chromatography (LC) fractionation. ExD is capable of producing a large number of structurally informative fragment ions for elucidation of structural details, complementary to collision-induced dissociation (CID). We first applied the selected accumulation-trapped IMS (SA-TIMS)-electronic excitation dissociation (EED) method to analyze various mixtures of glycan isomers. Glycan linkage isomers with linear or branched structure were successfully separated and subsequently identified. Theoretical modeling was also performed to gain a better understanding of isomer separation. The calculated collisional cross section (CCS) values match well with the experimentally measured ones, and suggested that the choice of metal charge carrier and charge state is critical for successful IMS separation of isomeric glycans. In addition, a SA-TIMS-electron capture dissociation (ECD) approach was employed to study gas-phase protein conformation, as the ECD fragmentation pattern is influenced by both the charge distribution and the presence of various non-covalent interactions. We demonstrated that different conformations of protein ions in a single charge state could produce distinct fragmentation pattern, presumably because of their differences in tertiary structures and/or proton locations. The second part describes characterization of glycoproteins using LC-hot ECD. To improve the cleavage coverage of glycopeptides, hot ECD, a fragmentation method utilizing the irradiation of high-energy electrons, was optimized for both middle-down and bottom-up analyses of glycopeptides, including peptides with multiple glycosylation sites. Hot ECD was shown to be an effective fragmentation technique for sequencing of glycopeptides, even for ions in lower charge states. In addition, the online LC-hot ECD approach was applied to characterize extensively modified glycoproteins from biological sources in which all glycosylation sites could be unambiguously determined. This study expands the applications of IMS, CID and ExD to structural analysis of various biomolecules, and explores the analytical potential of combining them for investigation of complex biological systems, in particular, enzyme mechanisms

The Affine Uncertainty Principle, Associated Frames and Applications in Signal Processing

Uncertainty relations play a prominent role in signal processing, stating that a signal can not be simultaneously concentrated in the two related domains of the corresponding phase space. In particular, a new uncertainty principle for the affine group, which is directly related to the wavelet transform has lead to a new minimizing waveform. In this thesis, a frame construction is proposed which leads to approximately tight frames based on this minimizing waveform. Frame properties such as the diagonality of the frame operator as well as lower and upper frame bounds are analyzed. Additionally, three applications of such frame constructions are introduced: inpainting of missing audio data, detection of neuronal spikes in extracellular recorded data and peak detection in MALDI imaging data