Biomimetic set up for chemosensor-based machine olfaction

The thesis falls into the field of machine olfaction and accompanying experimental set up for chemical gas sensing. Perhaps more than any other sensory modality, chemical sensing faces with major technical and conceptual challenges: low specificity, slow response time, long term instability, power consumption, portability, coding capacity and robustness. There is an important trend of the last decade pushing artificial olfaction to mimic the biological olfaction system of insects and mammalians. The designers of machine olfaction devices take inspiration from the biological olfactory system, because animals effortlessly accomplish some of the unsolved problems in machine olfaction. In a remarkable example of an olfactory guided behavior, male moths navigate over large distances in order to locate calling females by detecting pheromone signals both rapidly and robustly. The biomimetic chemical sensing aims to identify the key blocks in the olfactory pathways at all levels from the olfactory receptors to the central nervous system, and simulate to some extent the operation of these blocks, that would allow to approach the sensing performance known in biological olfactory system of animals. New technical requirements arise to the hardware and software equipment used in such machine olfaction experiments. This work explores the bioinspired approach to machine olfaction in depth on the technological side. At the hardware level, the embedded computer is assembled, being the core part of the experimental set up. The embedded computer is interfaced with two main biomimetic modules designed by the collaborators: a large-scale sensor array for emulation of the population of the olfactory receptors, and a mobile robotic platform for autonomous experiments for guiding olfactory behaviour. At the software level, the software development kit is designed to host the neuromorphic models of the collaborators for processing the sensory inputs as in the olfactory pathway. Virtualization of the set up was one of the key engineering solutions in the development. Being a device, the set up is transformed to a virtual system for running data simulations, where the software environment is essentially the same, and the real sensors are replaced by the virtual sensors coming from especially designed data simulation tool. The proposed abstraction of the set up results in an ecosystem containing both the models of the olfactory system and the virtual array. This ecosystem can loaded from the developed system image on any personal computer. In addition to the engineering products released in the course of thesis, the scientific results have been published in three journal articles, two book chapters and conference proceedings. The main results on validation of the set up under the scenario of robotic odour localization are reported in the book chapters. The series of three journal articles covers the work on the data simulation tool for machine olfaction: the novel model of drift, the models to simulate the sensor array data based on the reference data set, and the parametrized simulated data and benchmarks proposed for the first time in machine olfaction. This thesis ends up with a solid foundation for the research in biomimetic simulations and algorithms on machine olfaction. The results achieved in the thesis are expected to give rise to new bioinspired applications in machine olfaction, which could have a significant impact in the biomedical engineering research area.Esta tesis se enmarca en el campo de bioingeneria, mas particularmente en la configuración de un sistema experimental de sensores de gases químicos. Quizás más que en cualquier otra modalidad de sensores, los sensores químicos representan un conjunto de retos técnicos y conceptuales ya que deben lidiar con problemas como su baja especificidad, su respuesta temporal lenta, su inestabilidad a largo plazo, su alto consumo enérgético, su portabilidad, así como la necesidad de un sistema de datos y código robusto. En la última década, se ha observado una clara tendencia por parte de los sistemas de machine olfaction hacia la imitación del sistema de olfato biológico de insectos y mamíferos. Los diseñadores de estos sistemas se inspiran del sistema olfativo biológico, ya que los animales cumplen, sin apenas esfuerzo, algunos de los escenarios no resueltos en machine olfaction. Por ejemplo, las polillas machos recorren largas distancias para localizar las polillas hembra, detectando sus feromonas de forma rápida y robusta. La detección biomimética de gases químicos tiene como objetivo identificar los elementos fundamentales de la vía olfativa a todos los niveles, desde los receptores olfativos hasta el sistema nervioso central, y simular, en cierta medida, el funcionamiento de estos bloques, lo que permitiría acercar el rendimiento de la detección al rendimiento de los sistemas olfativos conociodos de los animales. Esto conlleva nuevos requisitos técnicos a nivel de equipamiento tanto hardware como software utilizado en este tipo de experimentos de machine olfaction. Este trabajo propone un enfoque bioinspirado para la ¿machine olfaction¿, explorando a fondo la parte tecnológica. A nivel hardware, un ordenador embedido se ha ensamblado, siendo ésta la parte más importante de la configuración experimental. Este ordenador integrado está interconectado con dos módulos principales biomiméticos diseñados por los colaboradores: una matriz de sensores a gran escala y una plataforma móvil robotizada para experimentos autónomos. A nivel software, el kit de desarrollo software se ha diseñado para recoger los modelos neuromórficos de los colaboradores para el procesamiento de las entradas sensoriales como en la vía olfativa biológica. La virtualización del sistema fue una de las soluciones ingenieriles clave de su desarrollo. Al ser un dispositivo, el sistema se ha transformado en un sistema virtual para la realización de simulaciones de datos, donde el entorno de software es esencialmente el mismo, y donde los sensores reales se sustituyen por sensores virtuales procedentes de una herramienta de simulación de datos especialmente diseñada. La propuesta de abstracción del sistema resulta en un ecosistema que contiene tanto los modelos del sistema olfativo como la matriz virtual . Este ecosistema se puede cargar en cualquier ordenador personal como una imagen del sistema desarrollado. Además de los productos de ingeniería entregados en esta tesis, los resultados científicos se han publicado en tres artículos en revistas, dos capítulos de libros y los proceedings de dos conferencias internacionales. Los principales resultados en la validación del sistema en el escenario de la localización robótica de olores se presentan en los capítulos del libro. Los tres artículos de revistas abarcan el trabajo en la herramienta de simulación de datos para machine olfaction: el novedoso modelo de drift, los modelos para simular la matriz de sensores basado en el conjunto de datos de referencia, y la parametrización de los datos simulados y los benchmarks propuestos por primera vez en machine olfaction. Esta tesis ofrece una base sólida para la investigación en simulaciones biomiméticas y en algoritmos en machine olfaction. Los resultados obtenidos en la tesis pretenden dar lugar a nuevas aplicaciones bioinspiradas en machine olfaction, lo que podría tener un significativo impacto en el área de investigación en ingeniería biomédic

Synthetic benchmarks for machine olfaction: Classification, segmentation and sensor damage

The design of the signal and data processing algorithms requires a validation stage and some data relevant for a validation procedure. While the practice to share public data sets and make use of them is a recent and still on-going activity in the community, the synthetic benchmarks presented here are an option for the researches, who need data for testing and comparing the algorithms under development. The collection of synthetic benchmark data sets were generated for classification, segmentation and sensor damage scenarios, each defined at 5 difficulty levels. The published data are related to the data simulation tool, which was used to create a virtual array of 1020 sensors with a default set of parametersPostprint (published version

The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes

Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i.e. the levels of coagulation pathway–related proteins). The resulting metaphenotypes integrate the information regarding the underlying biological process (i.e. thrombus/clot formation). Secondly, we take advantage of a family based Genome Wide Association Study to identify genetic elements influencing these metaphenotypes and consequently thrombosis risk. Our study utilized data from the GAIT Project (Genetic Analysis of Idiopathic Thrombophilia). We obtained 15 metaphenotypes, which showed significant heritabilities, ranging from 0.2 to 0.7. These results indicate the importance of genetic factors in the variability of these traits. We found 4 metaphenotypes that showed significant associations with SNPs. The most relevant were those mapped in a region near the HRG, FETUB and KNG1 genes. Our results are provocative since they show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation. Integrating data from multiple correlated measurements through metaphenotypes is a promising approach to elucidate the hidden genetic mechanisms underlying complex diseases.Postprint (published version

lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals.

BACKGROUND: Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models. Apart from applications in linkage studies of related individuals, such functionalities are of high interest for association studies in situations where multiple covariance matrices need to be modeled, a scenario not covered by many genome-wide association study (GWAS) software. RESULTS: To address the aforementioned limitations, we developed a new R package lme4qtl as an extension of lme4. First, lme4qtl contributes new models for genetic studies within a single tool integrated with lme4 and its companion packages. Second, lme4qtl offers a flexible framework for scenarios with multiple levels of relatedness and becomes efficient when covariance matrices are sparse. We showed the value of our package using real family-based data in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2) project. CONCLUSIONS: Our software lme4qtl enables QTL mapping models with a versatile structure of random effects and efficient computation for sparse covariances. lme4qtl is available at https://github.com/variani/lme4qtl

A software tool for large-scale synthetic experiments based on polymeric sensor arrays

This manuscript introduces a software tool that allows for the design of synthetic experiments in machine olfaction. The proposed software package includes both, a virtual sensor array that reproduces the diversity and response of a polymer array and tools for data generation. The synthetic array of sensors allows for the generation of chemosensor data with a variety of characteristics: unlimited number of sensors, support of multicomponent gas mixtures and full parametric control of the noise in the system. The artificial sensor array is inspired from a reference database of seventeen polymeric sensors with concentration profiles for three analytes. The main features in the sensor data, like sensitivity, diversity, drift and sensor noise, are captured by a set of models under simplified assumptions. The generator of sensor signals can be used in applications related to test and benchmarking of signal processing methods, neuromorphic simulations in machine olfaction and educational tools. The software is implemented in R language and can be freely accessed at: http://chemosensors.r-forge.r-project.org/

Bioinspired early detection through gas flow modulation in chemo-sensory systems

The design of bioinspired systems for chemical sensing is an engaging line of research in machine olfaction. Developments in this line could increase the lifetime and sensitivity of artificial chemo-sensory systems. Such approach is based on the sensory systems known in live organisms, and the resulting developed artificial systems are targeted to reproduce the biological mechanisms to some extent. Sniffing behaviour, sampling odours actively, has been studied recently in neuroscience, and it has been suggested that the respiration frequency is an important parameter of the olfactory system, since the odour perception, especially in complex scenarios such as novel odourants exploration, depends on both the stimulus identity and the sampling method. In this work we propose a chemical sensing system based on an array of 16 metal-oxide gas sensors that we combined with an external mechanical ventilator to simulate the biological respiration cycle. The tested gas classes formed a relatively broad combination of two analytes, acetone and ethanol, in binary mixtures. Two sets of low-frequency and high-frequency features were extracted from the acquired signals to show that the high-frequency features contain information related to the gas class. In addition, such information is available at early stages of the measurement, which could make the technique suitable in early detection scenarios. The full data set is made publicly available to the community. (C) 2014 Elsevier B.V. All rights reserved.Postprint (author's final draft

Bioinspired Early Detection through gas flow modulation in chemo-sensory systems

The design of bioinspired systems for chemical sensing is an engaging line of research in machine olfaction. Developments in this line could increase the lifetime and sensitivity of artificial chemo-sensory systems. Such approach is based on the sensory systems known in live organisms, and the resulting developed artificial systems are targeted to reproduce the biological mechanisms to some extent. Sniffing behaviour, sampling odours actively, has been studied recently in neuroscience, and it has been suggested that the respiration frequency is an important parameter of the olfactory system, since the odour perception, especially in complex scenarios such as novel odourants exploration, depends on both the stimulus identity and the sampling method. In this work we propose a chemical sensing system based on an array of 16 metal-oxide gas sensors that we combined with an external mechanical ventilator to simulate the biological respiration cycle. The tested gas classes formed a relatively broad combination of two analytes, acetone and ethanol, in binary mixtures. Two sets of low-frequency and high-frequency features were extracted from the acquired signals to show that the high-frequency features contain information related to the gas class. In addition, such information is available at early stages of the measurement, which could make the technique suitable in early detection scenarios. The full data set is made publicly available to the community

Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility