Resilient Bioinspired Algorithms: A Computer System Design Perspective

This preprint has not undergone peer review or any post-submission improvements or corrections. The Version of Record of this contribution is published in Cotta, C., Olague, G. (2022). Resilient Bioinspired Algorithms: A Computer System Design Perspective. In: Jiménez Laredo, J.L., Hidalgo, J.I., Babaagba, K.O. (eds) Applications of Evolutionary Computation. EvoApplications 2022. Lecture Notes in Computer Science, vol 13224. Springer, Cham. https://doi.org/10.1007/978-3-031-02462-7_39Resilience can be defined as a system's capability for returning to normal operation after having suffered a disruption. This notion is of the foremost interest in many areas, in particular engineering. We argue in this position paper that is is a crucial property for bioinspired optimization algorithms as well. Following a computer system perspective, we correlate some of the defining requirements for attaining resilient systems to issues, features, and mechanisms of these techniques. It is shown that bioinspired algorithms do not only exhibit a notorious built-in resilience, but that their plasticity also allows accommodating components that may boost it in different ways. We also provide some relevant research directions in this area.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Prescriptive formalism for constructing domain-specific evolutionary algorithms

It has been widely recognised in the computational intelligence and machine learning communities that the key to understanding the behaviour of learning algorithms is to understand what representation is employed to capture and manipulate knowledge acquired during the learning process. However, traditional evolutionary algorithms have tended to employ a fixed representation space (binary strings), in order to allow the use of standardised genetic operators. This approach leads to complications for many problem domains, as it forces a somewhat artificial mapping between the problem variables and the canonical binary representation, especially when there are dependencies between problem variables (e.g. problems naturally defined over permutations). This often obscures the relationship between genetic structure and problem features, making it difficult to understand the actions of the standard genetic operators with reference to problem-specific structures. This thesis instead advocates m..

Reflections on plague in African history (14th–19th c.)

In 1347, the western and Mediterranean parts of the Old World recorded the first outbreaks of a returning mortal disease that would make its presence felt over several centuries. Known today as the Second Plague Pandemic—a zoonosis due to the bacterium Yersinia pestis—it scythed between a third and half of the population without regard for wealth or status. It deeply transformed all facets of societies, ignited fears, violence, and pogroms, tested the flexibility of religions, hierarchies, and traditions, and excited ambitions. Although the plague is commonly described as a pandemic, historical knowledge about the initial Black Death and the many recurrent waves of the disease is largely restricted to Western Europe and the Mediterranean world, where the literate elite left an impressive documentary record that served as resource to the long-lasting and flourishing heuristic tradition of Plague Studies. If, as suggested by Monica Green, the concept of ‘pandemic’ is to be taken seriously, we must consider the many excluded parts of the Old World, and especially Africa, in our plague narratives. We must recognize that these societies that did not practise ‘the reduction of speech to graphic forms’—to use the expression coined by Jack Goody—also could have experienced the brutal mortality of the plague and its radical transformative power, while producing no organized and specific, long-lasting traces. By extension, we must also recognize that all literate societies that had in common the art of writing did not practise this art in the same way and may not have produced identical categories of documentary records. Cultural differences affect the nature of the documentary archive, as illustrated by literate practices in medieval Nubia and Ethiopia. The invisibility or limited visibility of the plague in the documentary record is, therefore, a challenge for historians and a disguised invitation to accept the absence of evidence as evidence of absence. This paper is my attempt to resist this temptation, to challenge the quasi-absence of interest in the plague problem in the historiography of Sub-Saharan Africa, and to lay out the foundation of a research strategy that will be multi-disciplinary and comparative. The plague problem is not a footnote to African history. If the plague impacted African societies as it did in documented parts of the Old World, we must have missed or misread fundamental processes of change it entailed. Would we understand and interpret the history of Western Europe or the Mediterranean as we do if we ignored that the plague had occurred? Here, I do not solve the plague conundrum in Sub-Saharan Africa; rather, I build on the persuasive arguments made by other contributors to this special issue about the presence of plague in different parts of Africa before the 19th century. My purpose is to propose multiple, critical, and cumulative—but far from exhaustive—pathways to reading and rereading the traditional and less traditional sources of African history in the light of the possibility of societal crises related to plague. Besides presenting fragments of evidence, this paper also serves as an introduction to three groundbreaking papers exploring the archaeological, documentary, and genomic sources of the disease in the African past

Cultural evolution of genetic heritability

Behavioral genetics and cultural evolution have both revolutionized our understanding of human behavior-largely independent of each other. Here we reconcile these two fields under a dual inheritance framework, offering a more nuanced understanding of the interaction between genes and culture. Going beyond typical analyses of gene-environment interactions, we describe the cultural dynamics that shape these interactions by shaping the environment and population structure. A cultural evolutionary approach can explain, for example, how factors such as rates of innovation and diffusion, density of cultural sub-groups, and tolerance for behavioral diversity impact heritability estimates, thus yielding predictions for different social contexts. Moreover, when cumulative culture functionally overlaps with genes, genetic effects become masked, unmasked, or even reversed, and the causal effects of an identified gene become confounded with features of the cultural environment. The manner of confounding is specific to a particular society at a particular time, but a WEIRD (Western, educated, industrialized, rich, democratic) sampling problem obscures this boundedness. Cultural evolutionary dynamics are typically missing from models of gene-to-phenotype causality, hindering generalizability of genetic effects across societies and across time. We lay out a reconciled framework and use it to predict the ways in which heritability should differ between societies, between socioeconomic levels and other groupings within some societies but not others, and over the life course. An integrated cultural evolutionary behavioral genetic approach cuts through the nature-nurture debate and helps resolve controversies in topics such as IQ

Investigación de la distribución de los alelos HLA en poblaciones sanas y enfermas mediante la aplicación de nuevas metodologías de secuenciación

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Inmunología, Oftalmología y ORL, leída el 09/03/2021Increasing our knowledge of the HLA system, including both the complete sequence description and the assessment of its diversity at the worldwide human population-level, is of great importance for elucidating the molecular functional mechanisms of the immune system and its regulation in health and disease. Furthermore, assessment of HLA allelic and haplotypic diversity of each human population is essential in the clinical histocompatibility and transplantation setting as well as in the pharmacogenetics, immunotherapy and anthropology fields. Nevertheless, the inherent vast polymorphism and high complexity presented by the HLA system have been an important challenge for its unambiguous and in-depth (high-resolution) characterization by previously available legacy molecular HLA genotyping methods (e.g. SSP, SSO and even SBT). Recent application of novel next-generation sequencing (NGS) technology for high-resolution molecular HLA genotyping has enabled to obtain, at a high-throughput mode and larger scale, full-length and/or extended sequences and genotypes of all major HLA genes, thus overcoming most of these previous limitations. Objectives: I) Characterization of HLA allele and haplotype diversity of all major classical HLA genes (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 and -DRB3/4/5) by application of NGS of a first representative cohort of the Spanish population that could also serve as a healthy control reference group. Respective statistical analyses were performed for this immunogenetic population data. II) Characterization of HLA allele and haplotype diversity of all major classical HLA genes (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 and -DRB3/4/5) by application of NGS of a respective cohort of multiple sclerosis (MS) patients in the Spanish population (recruited at the Department of Neurology, Hospital Clínic, Barcelona, Catalonia, Spain). A first case-control study was carried out to examine HLA-disease associations with MS in these Spanish population cohorts as well as to attempt a fine-mapping of these allele and haplotype associations by full gene resolution level via NGS. In addition, a second analysis exercise (i.e. test case) of this case-control study was carried out using an alternative healthy control group dataset, exclusively from the Spanish northeastern region of Catalonia in this second case, to evaluate possible differences in the findings of HLA-disease association with MS due to plausible regional HLA genetic variation within mainland Spain (i.e. as a statistical way to try controlling for any possible existing population stratification)...El estudio del sistema HLA, incluyendo la descripción completa de su secuencia y de la diversidad de este complejo HLA a nivel poblacional, es de gran importancia de cara a poder entender los mecanismos moleculares y funciones del sistema inmune así como su regulación en individuos sanos y enfermos. Además, la caracterización exhaustiva de la diversidad de alelos y haplotipos HLA de cada población humana es esencial en el campo de la inmunología de trasplante e histocompatibilidad al igual que en las áreas de farmacogenética e inmunoterapia. El inmenso polimorfismo y gran complejidad que presenta el sistema HLA han sido hasta ahora importantes barreras de cara a poder caracterizarlo en gran detalle (por alta resolución) y sin ambigüedades mediante métodos de genotipaje HLA tradicionales disponibles (como son SSP, SSO o incluso SBT). La reciente aplicación de la novedosa tecnología de secuenciación masiva NGS para el genotipaje molecular HLA por alta resolución ha posibilitado obtener secuencias completas o mucho más extendidas para genotipos de los principales genes de HLA, superándose así estas previas limitaciones. Objetivos: I) Caracterización de la diversidad alélica y haplotípica de los principales genes HLA (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 y -DRB3/4/5) mediante la aplicación de NGS en una primera cohorte representativa de la población española que, igualmente, constituirá una población control de referencia para estudios de asociación de HLA y enfermedades. También, respectivos análisis estadísticos se realizaron para estos resultados de genotipaje HLA. II) Caracterización de la diversidad alélica y haplotípica de los principales genes HLA (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1 y -DRB3/4/5) mediante la aplicación de NGS en una correspondiente cohorte de pacientes con esclerosis múltiple (EM) de la población española (reclutados y procedentes del Departamento de Neurología del Hospital Clínic (Barcelona, Cataluña)). Un primer estudio de asociación HLA tomando casos (pacientes EM) frente a controles sanos se llevó a cabo para examinar la asociación de genes HLA y la enfermedad de EM en estas cohortes de población española antes mencionadas. Así se buscaba realizar un mapeo fino de las respectivas asociaciones alélicas y haplotípicas de HLA mediante la gran resolución alélica proporcionada por esta metodología de secuenciación masiva. De modo adicional, y como un segundo ejercicio de análisis en este estudio de asociación HLA, se utilizó un grupo control sano alternativo al previo, que incluía individuos procedentes de la región de Cataluña (situada al noreste de España) exclusivamente en este caso, para evaluar así posibles diferencias dadas en la asociación de HLA con EM debido a la probable variación genética en HLA existente a nivel regional dentro del territorio de España...Fac. de MedicinaTRUEunpu

Sustainability through the Lens of Environmental Sociology

Our planet is undergoing radical environmental and social changes. Sustainability has now been put into question by, for example, our consumption patterns, loss of biodiversity, depletion of resources, and exploitative power relations. With apparent ecological and social limits to globalization and development, current levels of consumption are unsustainable, inequitable, and inaccessible to the majority of humans. Understanding and attaining sustainability is a crucial matter at a time when our planet is in peril—environmentally, economically, socially, and politically. Since its official inception in the 1970s, environmental sociology has provided a powerful lens to understanding the challenges, possibilities and modes of sustainability. Most chapters in this book were published as peer-reviewed articles in Sustainability in its special issue “Sustainability through the Lens of Environmental Sociology”, providing an environmental sociology approach to understanding and achieving the widely used notion of “sustainability.” This edited collection covers, among other topics, the inherent discursive formations of environmental sociology, conceptual tools and paradoxes, competing theories and practices, and their complex implications on our society at large. Chapters in this book specifically focus on how sustainable development has been understood through different theoretical lenses in environmental sociology, such as ecological modernization, policy/reformist sustainable development, and critical structural approaches (such as the treadmill of production, ecological Marxism, metabolic rift theory, etc.); and how sustainable development has been practiced in, or by, various stakeholders, such as states, corporations, and local communities, for various ends, through the use of specific case studies, showing, for example, the discursive shifts, dynamic formations, and diverse contours of sustainable development. The range of relevant topics includes: • Environmental sociology as a field of inquiry for sustainability • Historical context of sustainable development in environmental sociology • Nature-society relationship in environmental sociology • Theories/approaches to sustainability discourse in environmental sociology • Environmentalism/environmental movements for sustainability • Empirical cases (such as climate change, biodiversity, food, certification, etc.) through the lens of environmental sociolog

Inter-individual variation of the human epigenome & applications

Genome-wide association studies (GWAS) have led to the discovery of genetic variants influencing human phenotypes in health and disease. However, almost two decades later, most human traits can still not be accurately predicted from common genetic variants. Moreover, genetic variants discovered via GWAS mostly map to the non-coding genome and have historically resisted interpretation via mechanistic models. Alternatively, the epigenome lies in the cross-roads between genetics and the environment. Thus, there is great excitement towards the mapping of epigenetic inter-individual variation since its study may link environmental factors to human traits that remain unexplained by genetic variants. For instance, the environmental component of the epigenome may serve as a source of biomarkers for accurate, robust and interpretable phenotypic prediction on low-heritability traits that cannot be attained by classical genetic-based models. Additionally, its research may provide mechanisms of action for genetic associations at non-coding regions that mediate their effect via the epigenome. The aim of this thesis was to explore epigenetic inter-individual variation and to mitigate some of the methodological limitations faced towards its future valorisation.Chapter 1 is dedicated to the scope and aims of the thesis. It begins by describing historical milestones and basic concepts in human genetics, statistical genetics, the heritability problem and polygenic risk scores. It then moves towards epigenetics, covering the several dimensions it encompasses. It subsequently focuses on DNA methylation with topics like mitotic stability, epigenetic reprogramming, X-inactivation or imprinting. This is followed by concepts from epigenetic epidemiology such as epigenome-wide association studies (EWAS), epigenetic clocks, Mendelian randomization, methylation risk scores and methylation quantitative trait loci (mQTL). The chapter ends by introducing the aims of the thesis.Chapter 2 focuses on stochastic epigenetic inter-individual variation resulting from processes occurring post-twinning, during embryonic development and early life. Specifically, it describes the discovery and characterisation of hundreds of variably methylated CpGs in the blood of healthy adolescent monozygotic (MZ) twins showing equivalent variation among co-twins and unrelated individuals (evCpGs) that could not be explained only by measurement error on the DNA methylation microarray. DNA methylation levels at evCpGs were shown to be stable short-term but susceptible to aging and epigenetic drift in the long-term. The identified sites were significantly enriched at the clustered protocadherin loci, known for stochastic methylation in neurons in the context of embryonic neurodevelopment. Critically, evCpGs were capable of clustering technical and longitudinal replicates while differentiating young MZ twins. Thus, discovered evCpGs can be considered as a first prototype towards universal epigenetic fingerprint, relevant in the discrimination of MZ twins for forensic purposes, currently impossible with standard DNA profiling. Besides, DNA methylation microarrays are the preferred technology for EWAS and mQTL mapping studies. However, their probe design inherently assumes that the assayed genomic DNA is identical to the reference genome, leading to genetic artifacts whenever this assumption is not fulfilled. Building upon the previous experience analysing microarray data, Chapter 3 covers the development and benchmarking of UMtools, an R-package for the quantification and qualification of genetic artifacts on DNA methylation microarrays based on the unprocessed fluorescence intensity signals. These tools were used to assemble an atlas on genetic artifacts encountered on DNA methylation microarrays, including interactions between artifacts or with X-inactivation, imprinting and tissue-specific regulation. Additionally, to distinguish artifacts from genuine epigenetic variation, a co-methylation-based approach was proposed. Overall, this study revealed that genetic artifacts continue to filter through into the reported literature since current methodologies to address them have overlooked this challenge.Furthermore, EWAS, mQTL and allele-specific methylation (ASM) mapping studies have all been employed to map epigenetic variation but require matching phenotypic/genotypic data and can only map specific components of epigenetic inter-individual variation. Inspired by the previously proposed co-methylation strategy, Chapter 4 describes a novel method to simultaneously map inter-haplotype, inter-cell and inter-individual variation without these requirements. Specifically, binomial likelihood function-based bootstrap hypothesis test for co-methylation within reads (Binokulars) is a randomization test that can identify jointly regulated CpGs (JRCs) from pooled whole genome bisulfite sequencing (WGBS) data by solely relying on joint DNA methylation information available in reads spanning multiple CpGs. Binokulars was tested on pooled WGBS data in whole blood, sperm and combined, and benchmarked against EWAS and ASM. Our comparisons revealed that Binokulars can integrate a wide range of epigenetic phenomena under the same umbrella since it simultaneously discovered regions associated with imprinting, cell type- and tissue-specific regulation, mQTL, ageing or even unknown epigenetic processes. Finally, we verified examples of mQTL and polymorphic imprinting by employing another novel tool, JRC_sorter, to classify regions based on epigenotype models and non-pooled WGBS data in cord blood. In the future, we envision how this cost-effective approach can be applied on larger pools to simultaneously highlight regions of interest in the methylome, a highly relevant task in the light of the post-GWAS era.Moving towards future applications of epigenetic inter-individual variation, Chapters 5 and 6 are dedicated to solving some of methodological issues faced in translational epigenomics.Firstly, due to its simplicity and well-known properties, linear regression is the starting point methodology when performing prediction of a continuous outcome given a set of predictors. However, linear regression is incompatible with missing data, a common phenomenon and a huge threat to the integrity of data analysis in empirical sciences, including (epi)genomics. Chapter 5 describes the development of combinatorial linear models (cmb-lm), an imputation-free, CPU/RAM-efficient and privacy-preserving statistical method for linear regression prediction on datasets with missing values. Cmb-lm provide prediction errors that take into account the pattern of missing values in the incomplete data, even at extreme missingness. As a proof-of-concept, we tested cmb-lm in the context of epigenetic ageing clocks, one of the most popular applications of epigenetic inter-individual variation. Overall, cmb-lm offer a simple and flexible methodology with a wide range of applications that can provide a smooth transition towards the valorisation of linear models in the real world, where missing data is almost inevitable. Beyond microarrays, due to its high accuracy, reliability and sample multiplexing capabilities, massively parallel sequencing (MPS) is currently the preferred methodology of choice to translate prediction models for traits of interests into practice. At the same time, tobacco smoking is a frequent habit sustained by more than 1.3 billion people in 2020 and a leading (and preventable) health risk factor in the modern world. Predicting smoking habits from a persistent biomarker, such as DNA methylation, is not only relevant to account for self-reporting bias in public health and personalized medicine studies, but may also allow broadening forensic DNA phenotyping. Previously, a model to predict whether someone is a current, former, or never smoker had been published based on solely 13 CpGs from the hundreds of thousands included in the DNA methylation microarray. However, a matching lab tool with lower marker throughput, and higher accuracy and sensitivity was missing towards translating the model in practice. Chapter 6 describes the development of an MPS assay and data analysis pipeline to quantify DNA methylation on these 13 smoking-associated biomarkers for the prediction of smoking status. Though our systematic evaluation on DNA standards of known methylation levels revealed marker-specific amplification bias, our novel tool was still able to provide highly accurate and reproducible DNA methylation quantification and smoking habit prediction. Overall, our MPS assay allows the technological transfer of DNA methylation microarray findings and models to practical settings, one step closer towards future applications.Finally, Chapter 7 provides a general discussion on the results and topics discussed across Chapters 2-6. It begins by summarizing the main findings across the thesis, including proposals for follow-up studies. It then covers technical limitations pertaining bisulfite conversion and DNA methylation microarrays, but also more general considerations such as restricted data access. This chapter ends by covering the outlook of this PhD thesis, including topics such as bisulfite-free methods, third-generation sequencing, single-cell methylomics, multi-omics and systems biology.<br/