Bioinformatic tools for exposome data analysis : application to human molecular signatures of ultraviolet light effects
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González Ruiz, Juan Ramón
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174 p.
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Hernandez-Ferrer, C. Bioinformatic tools for exposome data analysis : application to human molecular signatures of ultraviolet light effects. Universitat Pompeu Fabra; 2017. handle: http://hdl.handle.net/10803/572046
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Programa de doctorat en Biomedicina
Abstract
Las enfermedades complejas se encuentran entre las más comunes y son causadas por una combinación de factores genéticos y ambientales (contaminación ambiental, estilo de vida, etc). Entre las enfermedades complejas que se pueden destacar se encuentran la obesidad, el asma, la hipertensión o la diabetes. Diversos estudios científicos sugieren que el hecho de padecer enfermedades complejas está condicionado a la aparición o acumulación de determinados factores ambientales. Asimismo, se ha descrito que los factores ambientales son unos de los principales contribuyentes a la carga mundial de morbilidad. Todo esto nos lleva a definir el término exposoma como el conjunto de factores ambientales a los que un individuo se ve expuesto desde la concepción hasta la muerte. El estudio de la mecánica subyacente que vincula el exposoma con la salud es un campo de investigación emergente con un fuerte potencial para proporcionar nuevos conocimientos sobre la etiología de las enfermedades. La primera parte de esta tesis se centra en la exposición a la radiación ultravioleta. La exposición a la radiación ultravioleta proviene de fuentes tanto naturales como artificiales. La radiación ultravioleta incluye tres subtipos de radiación según su longitud de onda (UVA 315-400 nm, UVB 315-295 nm y UVC 295-200 nm). Si bien la principal fuente natural de radiación ultravioleta es el Sol, la UVC no llega a la superficie de la Tierra debido a su absorción por la capa estratosférica de ozono. En consecuencia, la exposición a radiación ultravioleta a la que estamos usualmente sometidos consisten en una mezcla de UVA (95 %) y UVB (5 %). Los efectos de la radiación ultravioleta en humanos pueden ser beneficiosos o perjudiciales dependiendo de su cantidad y forma. Los efectos perjudiciales y agudos de la radiación ultravioleta incluyen eritema, oscurecimiento del pigmento, retraso en el bronceado y engrosamiento de la epidermis. Repetidas lesiones en la piel producidas por radiación ultravioleta pueden predisponer, en última instancia, a efectos crónicos de fotoenvejecimiento, inmunosupresión y fotocarcinogénesis. El mayor efecto beneficioso de la radiación ultravioleta es la síntesis cutánea de la vitamina D. La vitamina D es necesaria para mantener el calcio fisiológico y del fósforo para la mineralización ósea y para prevenir el raquitismo, la osteomalacia y la osteoporosis. El paradigma del exposoma es trabajar con múltiples exposiciones a la vez en vez centrarse en una sola exposición. Este enfoque permite tener una visión más parecida a la realidad que vivimos. Luego, la segunda parte se centra en las herramientas para explorar cómo caracterizar y analizar el exposoma y cómo probar sus efectos en múltiples capas biológicas intermedias para proporcionar información sobre los mecanismos moleculares subyacentes que vinculan las exposiciones ambientales a los resultados de salud.
Most common diseases are caused by a combination of genetic, environmental and lifestyle factors. These diseases are referred to as complex diseases. Examples of this type of diseases are obesity, asthma, hypertension or diabetes. Several empirical evidence suggest that exposures are necessary determinants of complex disease operating in a causal background of genetic diversity. Moreover, environmental factors have long been implicated as major contributors to the global disease burden. This leads to the formulation of the exposome, that contains any exposure to which an individual is subjected from conception to death. The study of the underlying mechanics that links the exposome with human health is an emerging research field with a strong potential to provide new insights into disease etiology. The first part of this thesis is focused on ultraviolet radiation (UVR) exposure. UVR exposure occurs from both natural and artificial sources. UVR includes three subtypes of radiation according to its wavelength (UVA 315-400 nm, UVB 315-295 nm, and UVC 295-200 nm). While the main natural source of UVR is the Sun, UVC radiation does not reach Earth's surface because of its absorption by the stratospheric ozone layer. Then, exposures to UVR typically consist of a mixture of UVA (95%) and UVB (5%). Effects of UVR on human can be both beneficial and detrimental, depending on the amount and form of UVR. Detrimental and acute effects of UVR include erythema, pigment darkening, delayed tanning and thickening of the epidermis. Repeated UVR-induced injury to the skin, may ultimately predispose one to the chronic effects photoaging, immunosuppression, and photocarcinogenesis. The beneficial effect of UVR is the cutaneous synthesis of vitamin D. Vitamin D is necessary to maintain physiologic calcium and phosphorous for normal bone mineralization and to prevent rickets, osteomalacia, and osteoporosis. But the exposome paradigm is to work with multiple exposures at a time and with one or more health outcomes rather focus in a single exposures analysis. This approach tends to be a more accurate snapshot of the reality that we live in complex environments. Then, the second part is focused on the tools to explore how to characterize and analyze the exposome and how to test its effects in multiple intermediate biological layers to provide insights into the underlying molecular mechanisms linking environmental exposures to health outcomes.
Most common diseases are caused by a combination of genetic, environmental and lifestyle factors. These diseases are referred to as complex diseases. Examples of this type of diseases are obesity, asthma, hypertension or diabetes. Several empirical evidence suggest that exposures are necessary determinants of complex disease operating in a causal background of genetic diversity. Moreover, environmental factors have long been implicated as major contributors to the global disease burden. This leads to the formulation of the exposome, that contains any exposure to which an individual is subjected from conception to death. The study of the underlying mechanics that links the exposome with human health is an emerging research field with a strong potential to provide new insights into disease etiology. The first part of this thesis is focused on ultraviolet radiation (UVR) exposure. UVR exposure occurs from both natural and artificial sources. UVR includes three subtypes of radiation according to its wavelength (UVA 315-400 nm, UVB 315-295 nm, and UVC 295-200 nm). While the main natural source of UVR is the Sun, UVC radiation does not reach Earth's surface because of its absorption by the stratospheric ozone layer. Then, exposures to UVR typically consist of a mixture of UVA (95%) and UVB (5%). Effects of UVR on human can be both beneficial and detrimental, depending on the amount and form of UVR. Detrimental and acute effects of UVR include erythema, pigment darkening, delayed tanning and thickening of the epidermis. Repeated UVR-induced injury to the skin, may ultimately predispose one to the chronic effects photoaging, immunosuppression, and photocarcinogenesis. The beneficial effect of UVR is the cutaneous synthesis of vitamin D. Vitamin D is necessary to maintain physiologic calcium and phosphorous for normal bone mineralization and to prevent rickets, osteomalacia, and osteoporosis. But the exposome paradigm is to work with multiple exposures at a time and with one or more health outcomes rather focus in a single exposures analysis. This approach tends to be a more accurate snapshot of the reality that we live in complex environments. Then, the second part is focused on the tools to explore how to characterize and analyze the exposome and how to test its effects in multiple intermediate biological layers to provide insights into the underlying molecular mechanisms linking environmental exposures to health outcomes.
Keywords
UVR, Llum ultraviolada, Transcriptoma, Expressió gènica, Micro RNA, Ultraviolet light, Transcriptome, Gene expression, Exposome, Exposoma
Subjects
575 - General genetics. General cytogenetics. Immunogenetics. Evolution. Phylogeny
Publisher
Universitat Pompeu Fabra
