Automated mass spectrometry-based metabolomics data processing by blind source separation methods

Una de les principals limitacions de la metabolòmica és la transformació de dades crues en informació biològica. A més, la metabolòmica basada en espectrometria de masses genera grans quantitats de dades complexes caracteritzades per la co-elució de compostos i artefactes experimentals. L'objectiu d'aquesta tesi és desenvolupar estratègies automatitzades basades en deconvolució cega del senyal per millorar les capacitats dels mètodes existents que tracten les limitacions de les diferents passes del processament de dades en metabolòmica. L'objectiu d'aquesta tesi és també desenvolupar eines capaces d'executar el flux de treball del processament de dades en metabolòmica, que inclou el preprocessament de dades, deconvolució espectral, alineament i identificació. Com a resultat, tres nous mètodes automàtics per deconvolució espectral basats en deconvolució cega del senyal van ser desenvolupats. Aquests mètodes van ser inclosos en dues eines computacionals que permeten convertir automàticament dades crues en informació biològica interpretable i per tant, permeten resoldre hipòtesis biològiques i adquirir nous coneixements biològics.Una de les principals limitacions de la metabolòmica és la transformació de dades crues en informació biològica. A més, la metabolòmica basada en espectrometria de masses genera grans quantitats de dades complexes caracteritzades per la co-elució de compostos i artefactes experimentals. L'objectiu d'aquesta tesi és desenvolupar estratègies automatitzades basades en deconvolució cega del senyal per millorar les capacitats dels mètodes existents que tracten les limitacions de les diferents passes del processament de dades en metabolòmica. L'objectiu d'aquesta tesi és també desenvolupar eines capaces d'executar el flux de treball del processament de dades en metabolòmica, que inclou el preprocessament de dades, deconvolució espectral, alineament i identificació. Com a resultat, tres nous mètodes automàtics per deconvolució espectral basats en deconvolució cega del senyal van ser desenvolupats. Aquests mètodes van ser inclosos en dues eines computacionals que permeten convertir automàticament dades crues en informació biològica interpretable i per tant, permeten resoldre hipòtesis biològiques i adquirir nous coneixements biològics.Una de las principales limitaciones de la metabolómica es la transformación de datos crudos en información biológica. Además, la metabolómica basada en espectrometría de masas genera grandes cantidades de datos complejos caracterizados por la co-elución de compuestos y artefactos experimentales. El objetivo de esta tesis es desarrollar estrategias automatizadas basadas en deconvolución ciega de la señal para mejorar las capacidades de los métodos existentes que tratan las limitaciones de los diferentes pasos del procesamiento de datos en metabolómica. El objetivo de esta tesis es también desarrollar herramientas capaces de ejecutar el flujo de trabajo del procesamiento de datos en metabolómica, que incluye el preprocessamiento de datos, deconvolución espectral, alineamiento e identificación. Como resultado, tres nuevos métodos automáticos para deconvolución espectral basados en deconvolución ciega de la señal fueron desarrollados. Estos métodos fueron incluidos en dos herramientas computacionales que permiten convertir automáticamente datos crudos en información biológica interpretable y por lo tanto, permiten resolver hipótesis biológicas y adquirir nuevos conocimientos biológicos.One of the major bottlenecks in metabolomics is to convert raw data samples into biological interpretable information. Moreover, mass spectrometry-based metabolomics generates large and complex datasets characterized by co-eluting compounds and with experimental artifacts. This thesis main objective is to develop automated strategies based on blind source separation to improve the capabilities of the current methods that tackle the different metabolomics data processing workflow steps limitations. Also, the objective of this thesis is to develop tools capable of performing the entire metabolomics workflow for GC--MS, including pre-processing, spectral deconvolution, alignment and identification. As a result, three new automated methods for spectral deconvolution based on blind source separation were developed. These methods were embedded into two computation tools able to automatedly convert raw data into biological interpretable information and thus, allow resolving biological answers and discovering new biological insights

Automated resolution of chromatographic signals by independent component analysis-orthogonal signal deconvolution in comprehensive gas chromatography/mass spectrometry-based metabolomics

Comprehensive gas chromatography-mass spectrometry (GC x GC-MS) provides a different perspective in metabolomics profiling of samples. However, algorithms for GCx GC-MS data processing are needed in order to automatically process the data and extract the purest information about the compounds appearing in complex biological samples. This study shows the capability of independent component analysis-orthogonal signal deconvolution (ICA-OSD), an algorithm based on blind source separation and distributed in an R package called osd, to extract the spectra of the compounds appearing in GCx GC-MS chromatograms in an automated manner. We studied the performance of ICA-OSD by the quantification of 38 metabolites through a set of 20 Jurkat cell samples analyzed by GCx GC-MS. The quantification by ICA-OSD was compared with a supervised quantification by selective ions, and most of the R2 coefficients of determination were in good agreement (R-2>0.90) while up to 24 cases exhibited an excellent linear relation (R-2>0.95). We concluded that ICA-OSD can be used to resolve co-eluted compounds in GC x GC-MS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Postprint (author's final draft

Radio Weak Gravitational Lensing with VLA and MERLIN

We carry out an exploratory weak gravitational lensing analysis on a combined VLA and MERLIN radio data set: a deep (3.3 micro-Jy beam^-1 rms noise) 1.4 GHz image of the Hubble Deep Field North. We measure the shear estimator distribution at this radio sensitivity for the first time, finding a similar distribution to that of optical shear estimators for HST ACS data in this field. We examine the residual systematics in shear estimation for the radio data, and give cosmological constraints from radio-optical shear cross-correlation functions. We emphasize the utility of cross-correlating shear estimators from radio and optical data in order to reduce the impact of systematics. Unexpectedly we find no evidence of correlation between optical and radio intrinsic ellipticities of matched objects; this result improves the properties of optical-radio lensing cross-correlations. We explore the ellipticity distribution of the radio counterparts to optical sources statistically, confirming the lack of correlation; as a result we suggest a connected statistical approach to radio shear measurements.Comment: 16 pages with 19 figures, accepted for publication in MNRAS; Minor corrections to section 6.3; 2 references adde

Investigating parallel multi-step vibration processing pipelines for planetary stage fault detection in wind turbine drivetrains

This paper proposes a signal processing approach for wind turbine gearbox vibration signals based on employing multiple analysis pipelines. These so-called pipelines consist of combinations of various advanced signal processing methods that have been proven to be effective in literature when applied to wind turbine vibration signals. The performance of the pipelines is examined on vibration data containing different wind turbine gearbox faults in the planetary stages. Condition indicators are extracted from every pipeline to evaluate the fault detection capability for such incipient failures. The results indicate that the multipronged approach with the different pipelines increases the reliability of successfully detecting incipient planetary stage gearbox faults. The type, location, and severity of the fault influences the choice for the appropriate processing method combination. It is therefore often insufficient to only utilize a single processing pipeline for vibration analysis of wind turbine gearbox faults. Besides investigating the performance of the different processing techniques, the main outcome and recommendation of this paper is thus to employ a diversified analysis methodology which is not limited to a sole method combination, to improve the early detection rate of planetary stage gearbox faults

Development of 1H-NMR Serum Profiling Methods for High-Throughput Metabolomics

El perfilat de sèrum per ressonància magnètica nuclear de protó (1H-RMN) està especialment indicat per a anàlisi a gran escala en estudis epidemiològics, nutricionals o farmacològics. L’espectroscòpia 1H-RMN requereix mínima manipulació de mostra i gràcies a la seva resposta quantitativa permet la comparació directa entre laboratoris. Un perfilat complet de sèrum per 1H-RMN requereix de tres mesures que es corresponen amb tres espècies moleculars diferents: lipoproteïnes, metabòlits de baix pes molecular i lípids. El perfilat de sèrum per 1H-RMN permet obtenir informació de grandària, nombre de partícules i contingut lipídic de les subfraccions lipoproteiques, així com l'abundància d'aminoàcids, productes de la glicòlisi, cossos cetònics, àcids grassos i fosfolípids, entre d'altres. No obstant això, la complexitat espectral afavoreix la inclusió d'errors en l'anàlisi manual de les dades, mentre que les múltiples interaccions moleculars en el sèrum comprometen la seva precisió quantitativa. És per tant necessari desenvolupar mètodes robustos de perfilat metabòlic per consolidar la 1H-RMN en la pràctica clínica. Per a això, aquesta tesi presenta diverses estratègies metodològiques i computacionals. En el primer treball, es van desenvolupar mètodes de regressió dels lípids del perfil lipídic clàssic, generalitzables a mostres de població sana i amb valors de lípids i lipoproteïnes anormals. Aquests lípids representen els principals indicadors de risc cardiovascular i els objectius terapèutics primaris. En el segon estudi caracteritzem els errors de quantificació en el perfilat 1H-RMN de metabòlits clínicament rellevants, que són deguts a la seva agregació a la proteïna sanguínia. També proposem un mètode que fomenta la competició per l'agregació i que ens permet obtenir quantificacions dels nostres metabòlits properes a les absolutes. Finalment, el tercer treball presenta LipSpin: una eina bioinformàtica de codi obert específicament dissenyada per al perfilat de lípids per 1H-RMN. A més, aquest estudi exposa alguns aspectes metodològics per millorar l'anàlisi de lípids per RMN.El perfilado de suero por resonancia magnética nuclear de protón (1H-RMN) está especialmente indicado para el análisis a gran escala en estudios epidemiológicos, nutricionales o farmacológicos. La espectroscopía 1H-RMN requiere mínima manipulación de muestra y gracias a su respuesta cuantitativa permite la comparación directa entre laboratorios. Un perfilado completo de suero por 1H-RMN requiere de tres mediciones que se corresponden con tres especies moleculares distintas: lipoproteínas, metabolitos de bajo peso molecular y lípidos. El perfilado de suero por 1H-RMN permite obtener información de tamaño, número de partículas y contenido lipídico de las subfracciones lipoproteicas, así como la abundancia de aminoácidos, productos de la glicólisis, cuerpos cetónicos, ácidos grasos y fosfolípidos, entre otros. Sin embargo, la complejidad espectral favorece la inclusión de errores en el análisis manual de los datos, mientras que las múltiples interacciones moleculares en el suero comprometen su precisión cuantitativa. Es por tanto necesario desarrollar métodos robustos de perfilado metabólico para consolidar la 1H-RMN en la práctica clínica. Para ello, esta tesis presenta varias estrategias metodológicas y computacionales. En el primer trabajo, se desarrollaron métodos de regresión de los lípidos del perfil lipídico clásico, generalizables a muestras de población sana y con valores de lípidos y lipoproteínas anormales. Estos lípidos representan los principales indicadores de riesgo cardiovascular y los objetivos terapéuticos primarios. En el segundo estudio caracterizamos los errores de cuantificación en el perfilado 1H-RMN de metabolitos clínicamente relevantes, que son debidos a su agregación a la proteína sanguínea. También proponemos un método que fomenta la competición por la agregación y que nos permite obtener cuantificaciones de nuestros metabolitos cercanas a las absolutas. Por último, el tercer trabajo presenta LipSpin: una herramienta bioinformática de código abierto específicamente diseñada para el perfilado de lípidos por 1H-RMN. Además, este estudio expone algunos aspectos metodológicos para mejorar el análisis de lípidos por RMN.1H-NMR serum profiling is especially suitable for high-throughput epidemiological studies and large-scale nutritional studies and drug monitoring. It requires minimal sample manipulation and its quantitative response allows inter-laboratory comparison. A comprehensive 1H-NMR serum profiling consists of three measurements encoding different molecular species: lipoproteins, low-molecular-weight metabolites and lipids. 1H-NMR serum profiling provides information of size, particle number and lipid content of lipoprotein subclasses, as well as abundance of amino acids, glycolysis-related metabolites, ketone bodies, fatty acids and phospholipids, among others. However, the spectral complexity promotes errors in manual data analysis and the multiple molecular interactions within the sample compromise reliable quantifications. Developing robust methods of metabolite serum profiling is therefore desirable to consolidate high-throughput 1H-NMR in the clinical practice. This thesis presents several methodological and computational strategies to that end. In the first study, we developed generalizable regression methods for lipids in routine clinical practice (known as “lipid panel”), to be applied in healthy population and in a wide spectrum of lipid and lipoprotein abnormalities. These standard lipids are still the main measurements of cardiovascular risk and therapy targets. In the second study, we characterised the quantitative errors introduced by protein binding in 1H-NMR profiling of clinically-relevant LMWM in native serum. Then, we proposed a competitive binding strategy to achieve quantifications closer to absolute concentrations, being fully compatible with high-throughput NMR. Finally, the third study presents LipSpin: an open source bioinformatics tool specifically designed for 1H-NMR profiling of serum lipids. Moreover, some methodological aspects to improve NMR-based serum lipid analysis are discussed

Modulation Transfer Function Compensation Through A Modified Wiener Filter For Spatial Image Quality Improvement.

Kebergunaan data imej yang diperolehi dari suatu sensor pengimejan amat bergantung kepada keupayaan sensor tersebut untuk meresolusikan perincian spatial ke satu tahap yang boleh diterima. The usefulness of image data acquired from an imaging sensor critically depends on the ability of the sensor to resolve spatial details to an acceptable level

Improving Maternal and Fetal Cardiac Monitoring Using Artificial Intelligence

Early diagnosis of possible risks in the physiological status of fetus and mother during pregnancy and delivery is critical and can reduce mortality and morbidity. For example, early detection of life-threatening congenital heart disease may increase survival rate and reduce morbidity while allowing parents to make informed decisions. To study cardiac function, a variety of signals are required to be collected. In practice, several heart monitoring methods, such as electrocardiogram (ECG) and photoplethysmography (PPG), are commonly performed. Although there are several methods for monitoring fetal and maternal health, research is currently underway to enhance the mobility, accuracy, automation, and noise resistance of these methods to be used extensively, even at home. Artificial Intelligence (AI) can help to design a precise and convenient monitoring system. To achieve the goals, the following objectives are defined in this research: The first step for a signal acquisition system is to obtain high-quality signals. As the first objective, a signal processing scheme is explored to improve the signal-to-noise ratio (SNR) of signals and extract the desired signal from a noisy one with negative SNR (i.e., power of noise is greater than signal). It is worth mentioning that ECG and PPG signals are sensitive to noise from a variety of sources, increasing the risk of misunderstanding and interfering with the diagnostic process. The noises typically arise from power line interference, white noise, electrode contact noise, muscle contraction, baseline wandering, instrument noise, motion artifacts, electrosurgical noise. Even a slight variation in the obtained ECG waveform can impair the understanding of the patient's heart condition and affect the treatment procedure. Recent solutions, such as adaptive and blind source separation (BSS) algorithms, still have drawbacks, such as the need for noise or desired signal model, tuning and calibration, and inefficiency when dealing with excessively noisy signals. Therefore, the final goal of this step is to develop a robust algorithm that can estimate noise, even when SNR is negative, using the BSS method and remove it based on an adaptive filter. The second objective is defined for monitoring maternal and fetal ECG. Previous methods that were non-invasive used maternal abdominal ECG (MECG) for extracting fetal ECG (FECG). These methods need to be calibrated to generalize well. In other words, for each new subject, a calibration with a trustable device is required, which makes it difficult and time-consuming. The calibration is also susceptible to errors. We explore deep learning (DL) models for domain mapping, such as Cycle-Consistent Adversarial Networks, to map MECG to fetal ECG (FECG) and vice versa. The advantages of the proposed DL method over state-of-the-art approaches, such as adaptive filters or blind source separation, are that the proposed method is generalized well on unseen subjects. Moreover, it does not need calibration and is not sensitive to the heart rate variability of mother and fetal; it can also handle low signal-to-noise ratio (SNR) conditions. Thirdly, AI-based system that can measure continuous systolic blood pressure (SBP) and diastolic blood pressure (DBP) with minimum electrode requirements is explored. The most common method of measuring blood pressure is using cuff-based equipment, which cannot monitor blood pressure continuously, requires calibration, and is difficult to use. Other solutions use a synchronized ECG and PPG combination, which is still inconvenient and challenging to synchronize. The proposed method overcomes those issues and only uses PPG signal, comparing to other solutions. Using only PPG for blood pressure is more convenient since it is only one electrode on the finger where its acquisition is more resilient against error due to movement. The fourth objective is to detect anomalies on FECG data. The requirement of thousands of manually annotated samples is a concern for state-of-the-art detection systems, especially for fetal ECG (FECG), where there are few publicly available FECG datasets annotated for each FECG beat. Therefore, we will utilize active learning and transfer-learning concept to train a FECG anomaly detection system with the least training samples and high accuracy. In this part, a model is trained for detecting ECG anomalies in adults. Later this model is trained to detect anomalies on FECG. We only select more influential samples from the training set for training, which leads to training with the least effort. Because of physician shortages and rural geography, pregnant women's ability to get prenatal care might be improved through remote monitoring, especially when access to prenatal care is limited. Increased compliance with prenatal treatment and linked care amongst various providers are two possible benefits of remote monitoring. If recorded signals are transmitted correctly, maternal and fetal remote monitoring can be effective. Therefore, the last objective is to design a compression algorithm that can compress signals (like ECG) with a higher ratio than state-of-the-art and perform decompression fast without distortion. The proposed compression is fast thanks to the time domain B-Spline approach, and compressed data can be used for visualization and monitoring without decompression owing to the B-spline properties. Moreover, the stochastic optimization is designed to retain the signal quality and does not distort signal for diagnosis purposes while having a high compression ratio. In summary, components for creating an end-to-end system for day-to-day maternal and fetal cardiac monitoring can be envisioned as a mix of all tasks listed above. PPG and ECG recorded from the mother can be denoised using deconvolution strategy. Then, compression can be employed for transmitting signal. The trained CycleGAN model can be used for extracting FECG from MECG. Then, trained model using active transfer learning can detect anomaly on both MECG and FECG. Simultaneously, maternal BP is retrieved from the PPG signal. This information can be used for monitoring the cardiac status of mother and fetus, and also can be used for filling reports such as partogram

Artificial Intelligence for reverse engineering: application to detergents using Raman spectroscopy

The reverse engineering of a complex mixture, regardless of its nature, has become significant today. Being able to quickly assess the potential toxicity of new commercial products in relation to the environment presents a genuine analytical challenge. The development of digital tools (databases, chemometrics, machine learning, etc.) and analytical techniques (Raman spectroscopy, NIR spectroscopy, mass spectrometry, etc.) will allow for the identification of potential toxic molecules. In this article, we use the example of detergent products, whose composition can prove dangerous to humans or the environment, necessitating precise identification and quantification for quality control and regulation purposes. The combination of various digital tools (spectral database, mixture database, experimental design, Chemometrics / Machine Learning algorithm{\ldots}) together with different sample preparation methods (raw sample, or several concentrated / diluted samples) Raman spectroscopy, has enabled the identification of the mixture's constituents and an estimation of its composition. Implementing such strategies across different analytical tools can result in time savings for pollutant identification and contamination assessment in various matrices. This strategy is also applicable in the industrial sector for product or raw material control, as well as for quality control purposes