50 research outputs found
Explainable artificial intelligence to predict and identify prostate cancer tissue by gene expression
This work was supported by the ERDF and the Ministry of Economy, Innovation and Science of the Regional Government of Andalusia (grant number P18-RT-2248)Background and Objective: Prostate cancer is one of the most prevalent forms of cancer in men worldwide. Traditional screening strategies such as serum PSA levels, which are not necessarily cancer-specific, or digital rectal exams, which are often inconclusive, are still the screening methods used for the disease. Some studies have focused on identifying biomarkers of the disease but none have been reported for diagnosis in routine clinical practice and few studies have provided tools to assist the pathologist in the decision-making process when analyzing prostate tissue. Therefore, a classifier is proposed to predict the occurrence of PCa that provides physicians with accurate predictions and understandable explanations.
Methods: A selection of 47 genes was made based on differential expression between PCa and normal tissue, GO gene ontology as well as the literature to be used as input predictors for different machine learning methods based on eXplainable Artificial Intelligence. These methods were trained using different class-balancing strategies to build accurate classifiers using gene expression data from 550 samples from ’The Cancer Genome Atlas’. Our model was validated in four external cohorts with different ancestries, totaling 463 samples. In addition, a set of SHapley Additive exPlanations was provided to help clinicians understand the underlying reasons for each decision.
Results: An in-depth analysis showed that the Random Forest algorithm combined with majority class downsampling was the best performing approach with robust statistical significance. Our method achieved an average sensitivity and specificity of 0.90 and 0.8 with an AUC of 0.84 across all databases. The relevance of DLX1, MYL9 and FGFR genes for PCa screening was demonstrated in addition to the important role of novel genes such as CAV2 and MYLK.
Conclusions: This model has shown good performance in 4 independent external cohorts of different ancestries and the explanations provided are consistent with each other and with the literature, opening a horizon for its application in clinical practice. In the near future, these genes, in combination with our model, could be applied to liquid biopsy to improve PCa screening.European Union (EU)Ministry of Econ-omy, Innovation and Science of the Regional Government of Andalusia
P18-RT-224
Genetic structure in the paternal lineages of South East Spain revealed by the analysis of 17 Y-STRs
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-41580-9.The content of this article is part of the Ph.D. thesis of María Saiz which was conducted at the University of
Granada under the doctoral programme “Biomedicine”. The authors thank all of the participants who donated
buccal swabs and all those who helped in the sample collection—namely, María Luisa Aceituno Villalva, Leticia
Olga Rubio Lamia, and Verónica Delgado López. In addition, the authors want to thank Xiomara Gálvez for the
technical assistance in the laboratory.The genetic data of 17 Y chromosome short tandem repeats in 146 unrelated donor residents in the provinces of Granada, Málaga, and Almería (GMA) were analyzed to determine the genetic legacy of the male inhabitants of the former Kingdom of Granada. A total of 139 unique haplotypes were identified. Observed allele frequencies and haplogroup frequencies were also analyzed. By AMOVA and STRUCTURE analysis, the populations of the 3 provinces could be treated genetically as a single population. The most frequent haplogroup was R1b1b2 (58.22%). By network analysis of all individuals, we observed a distribution according to haplogroup assignment. To improve the characterization of GMA population, it was compared with those of North Africa, the Iberian Peninsula, and southern Europe. In our analysis of allele frequencies and genetic distances, the GMA population lay within the Spanish population group. Further, in the STRUCTURE analysis, there was no African component in the GMA population, confirming that, based on our genetic markers, the GMA population does not reflect any male genetic influence of the North African people. The presence of African haplogroups in the GMA population is irrelevant when their frequency is compared with those in other European populations
Overdamped deterministic ratchets driven by multifrequency forces
Presented at the XVIII Marian Smoluchowski Symposium on Statistical Physics, Zakopane, Poland, September 3–6, 2005We investigate a dissipative, deterministic ratchet model in the overdamped regime driven by a rectangular force. Extensive numerical calculations are presented in a diagram depicting the drift velocity as a function of a wide range of the driving parameter values. We also present some theoretical considerations which explain some features of the mentioned diagram. In particular, we proof the existence of regions in the driving parameter space with bounded particle motion possessing zero current. Moreover, we present an explicit analytical expression for the drift velocity in the adiabatic limit.Ministerio de Educación y Ciencia of Spain (FIS2005-02884) and the Junta de Andalucía. Also acknowledges the Ministerio de Educación y Ciencia o f Spain for a contract under the Juan de la Cierva program
EL ADN ANTIGUO UNA HERRAMIENTA PARA DESCIFRAR LA HISTORIA
The evolution of biomolecular techniques, as the PCR; has improved the quality of genetic analysis in f ields like forensic science and biomedicine. To these days, it is possible to obtain DNA from extinguished species; called ancient DNA (aDNA). The analysis of aDNA has been really helpful in anthropology and forensic sciences. Some important historical cases have been elucidated through these techniques as the identif ication of remains of Christopher Columbus and the Romanov dynasty. The main aim of this paper is to introduce in detail ancient DNA, its applications and the main advantages and disadvantages of working with this type of DNA.Gracias a la evolución de las técnicas biomoleculares como la PCR, campos como la medicina forense y la biomedicina han mejorado la calidad de los análisis genéticos. Actualmente, incluso es posible obtener ADN de especies ya extinguidas; este tipo de ADN se llama ADN antiguo (aDNA). El análisis del aDNA ha sido de gran ayuda en la antropología y la ciencia forense. Importantes casos históricos han sido resueltos gracias a este tipo de técnicas como la identif icación de los restos óseos de Cristóbal Colón y la dinastía Romanov entre otros. El principal objetivo de este artículo es hacer una introducción detallada del aDNA, sus aplicaciones y las principales ventajas e inconvenientes que se encuentran al trabajar con este tipo de ADN
Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review
Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA
has recently come under pressure, it is being replaced by compounds very similar in structure, but
data on the occurrence of these BPA analogues in food and human matrices are limited. The main
objective of this work was to investigate human exposure to BPA and analogues and the associated
health effects. We performed a literature review of the available research made in humans, in in vivo
and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact
on human health, especially in terms of obesity and other adverse health effects in children.This research was funded by Plan Estatal de I+D+I 2013-2016 Proyecto cofinanciado
FEDER-ISCIII PI17/01758 and by Fundación Mapfre MAPFRE2018
Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project
This work was supported by the Spanish Ministry of Economy and Competitiveness (I + D+i DEP2010-15639, I + D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.), the Spanish Ministry of Education (FPU13/03410 to D.S.-T.; FPU15/0002 to B.G.-C.), the Consejeria de Turismo, Comercio y Deporte, Junta de Andalucia (CTCD-201000019242-TRA to M.D.-F.), the Consejeria de Salud, Junta de Andalucia (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.Objectives. It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility
and environmental factors such as engaging in physical activity (PA), and that pain-related cognitions are also
important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate
genes) and the gene–gene, gene–PA and gene–sedentary behaviour interactions with pain and pain-related
cognitions in women with FM.
Methods. Saliva samples from 274 women with FM [mean (S.D.) age 51.7 (7.7) years] were collected for extracting
DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires,
and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis
was also performed.
Results. The rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually
related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid
receptor l gene, OPRM1) was related to pain catastrophizing. Five gene–behaviour interactions were significant:
the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular
body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale
of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and
severity of FM symptoms (codominant model, P-value 0.032).
Conclusion. The HTR2A gene (individually), COMT and OPRM1 gene–gene interaction, and the interactions
of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related
outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene–
sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should
examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic
susceptibility to pain.Spanish Government I + D+i DEP2010-15639
I + D+i DEP2013-40908-R
BES-2014-067612
FPU13/03410
FPU15/0002Junta de Andalucia CTCD-201000019242-TRA
PI-0520-2016University of Granada, Plan Propio de InvestigacionUnit of Excellence on Exercise and Health (UCEES
Identification of MiRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer
MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of
several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium
transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such
as miR-miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b,
with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and
TaqMan™ specific probes for amplification, we performed miRNAs’ analysis of 159 PC fresh tissues
and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA,
Gleason, TNM, and D’Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome
Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness
in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are
the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according
with our results, miR93-5p seems the most promising non-invasive biomarker for PC. To sum up,
miR-210-3p, miR-23c, miR-592, and miR93-5p miRNAs are suggested to be potential biomarkers
for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in
precision medicine for PC management.Regional Ministry of Health and Families of the
Andalusian Government (ref: PI-0319-2018)FIBAO (Andalusian Public Foundation
for Biomedical Research in Eastern Andalusia, “Alejandro Otero”
The influence of nutritional factors on prostate cancer incidence and aggressiveness
There is an increasing evidence for a link between nutrition, lifestyle and prostate cancer (PCa) development and/or progression of disease. The objective of this study was to examine the association between dietary factors and PCa incidence and aggressiveness in a case-control study. After the analysis of the anatomic pathology, subjects were classified in patients with PCa (n = 157) and controls (n = 158). Clinical data including Gleason score, PSA values and biopsy results, were compiled. Frequencies of food consumption and sociodemographic data were also obtained. The results showed that physical activity was significantly higher in control (p <.022). It was also found that some nutritional habits offer a protective effect among studied subjects, like high nuts (p =.041) and fish (p =.041) intakes. Moreover, there was a significant reduction in risk (p =.029) in cases with a higher fruits and vegetables intakes. A decreased risk of aggressive PCa was associated with fruits, vegetables, legumes and fish intakes. However, these relationships were not statistically significant when data were adjusted for covariates. In conclusion, this study found an inverse association between PCa risk and the intake of fruits and vegetables, fish and nuts. The results suggested that a diet with higher intakes of these foods as Mediterranean diet may lower the risk of PCa in the studied population. As dietary factors are modifiable, identifying food groups or dietary patterns that modulate the risk of PCa and its aggressiveness can offer effective and practical strategies for its primary prevention
Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness
This study is partially supported by ID#53169721 project funded by Pfizer and the exosomes characterization was financed thanks to the grant PY20_00241 (FEDER/Junta de Andalucia-Regional Ministry of Economic Transformation, Industry, Knowledge and Universities).Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio (TM) 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values <= 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.Pfizer 53169721FEDER/Junta de Andalucia-Regional Ministry of Economic Transformation, Industry, Knowledge and Universities PY20_0024
Uso de herramientas digitales como innovación de la docencia en Bioquímica y Biología Molecular. Un acercamiento de la Investigación a la Docencia
Gracias a proyectos de innovación docente previos donde realzamos y acercamos el papel de las herramientas de biología molecular y/o bioquímica al alumnado, nos ha surgido la idea de implementar este proyecto. Sabemos que las habilidades científico-técnicas adquiridas por la asignatura de Bioquímica, son cada vez más demandas en el sector empresarial, tanto para optar a un trabajo como para poder conocer/comprender metodologías necesarias para alguna estrategia transversal que deba desarrollarse en el mismo. La dificultad de una enseñanza práctica utilizando las tecnologías más novedosas empleadas en el momento actual, debido a su exclusividad, su elevado coste y los tiempos de espera en los arduos protocolos, se vence con el empleo de nuevas herramientas educativas e innovadoras que vamos a emplear en este proyecto, que además hemos intentado que sean atractivas y accesibles para el alumnado. Queremos tener a nuestro alumnado interesado en la asignatura de Bioquímica y para ello vamos a realizar varias acciones: 1) incorporar una visión transversal en varias asignaturas donde se vea la importancia de la bioquímica en distintas áreas como son la nutrición y la microbiología, muy enfocadas al sector Biosanitario, 2) acercar la investigación realizada en la UGR y su relación con la bioquímica, para que el alumnado vea este hecho como cercano, 3) usar herramientas digitales atractivas para motivar a los alumnos y facilitar el proceso de enseñanza-aprendizaje. Para ello, vamos a usar una herramienta muy empleada actualmente por los jóvenes como es la red social TikTok para difundir el material desarrollado, además de Podcast y así fomentar el interés en los alumnos por temas de biología molecular. Con esto buscamos desarrollar modelos de estudio más atractivos y dinámicos para nuestro estudiantado, que aumenten su interés y motivación y que les facilite su inserción laboral. Este proyecto será realizado por profesorado perteneciente a diferentes Departamentos, que imparte docencia en distintos Grados y Campus (Granada), por lo que va a permitir establecer nuevas redes docentes colaborativas.The idea for this project came from previous teaching innovation projects in which we have enhanced the role of molecular biology and/or biochemistry tools and brought them closer to students. We know that the scientific-technical skills acquired in Biochemistry are increasingly in demand in the business world, both to apply for a job and to know/understand the methodologies necessary to develop a transversal strategy in the same field. The difficulty of practical teaching using the latest technologies currently in use, due to their exclusivity, high cost and waiting times in tedious protocols, is overcome by the use of new and innovative teaching tools, which we will use in this project and which we have also tried to make attractive and accessible to students. We want our students to be interested in biochemistry, and to achieve this we will carry out several actions: 1) incorporate a transversal vision in several subjects where the importance of biochemistry in different areas such as nutrition and microbiology, very focused on the biosanitary sector, 2) bring the research carried out at the UGR and its relationship with biochemistry so that students see this fact as close, 3) use attractive digital tools to motivate students and facilitate the teaching-learning process. To this end, we will use a tool that is currently widely used by young people, such as the social network TikTok, to disseminate the material developed, as well as podcasts, in order to stimulate students' interest in molecular biology topics. The aim is to develop more attractive and dynamic study models for our students, which will increase their interest and motivation and facilitate their entry into the labour market. This project will be carried out by teachers from different departments, teaching in different courses and on different campuses (Granada), which will allow us to establish new collaborative teaching methods