Two GenomeWide SNP 6.0 (Affymetrix) samples. Left with a mosaic event, UPD, on chromosome 13. Right with a mosaic event, deletion, on chromosome 20. Measures seen in the plots corresponds to the LRR (black) and BAF (red).

Bioinformatic Tools for Exposome Data Analysis: Application to Human Molecular Signatures of Ultraviolet Light Effects

Summary

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.

Results

This project currenlty resulted in a publication at BMC Bioinformatics:

MultiDataSet: an R package for encapsulating multiple data sets with application to omic data integration Carles Hernandez-Ferrer, Carlos Ruiz-Arenas, Alba Beltran-Gomila and Juan R. González BMC Bioinformatics 2017 | doi:10.1186/s12859-016-1455-1

And apublication at Environmental Research:

The acute effects of ultraviolet radiation on the blood transcriptome are independent of plasma 25OHD3 Bustamante M, Hernandez-Ferrer C, Sarria Y, Harrison GI, Nonell L, Kang W, Friedländer MR, Estivill X, González JR, Nieuwenhuijsen M, Young AR. Environmental Research 2017 | doi: 10.1016/j.envres.2017.07.045