Testing the existence of an unadmixed ancestor from a specific population t generations ago

Datos y códigos en: https://figshare.com/articles/dataset/Testing_the_existence_of_an_unadmixed_ancestor_from_a_specific_population_t_The ancestry of each locus of the genome can be estimated (local ancestry) based on sequencing or genotyping information together with reference panels of ancestral source populations. The length of those ancestry-specific genomic segments are commonly used to understand migration waves and admixture events. In short time scales, it is often of interest to determine the existence of the most recent unadmixed ancestor from a specific population t generations ago. We built a hypothesis test to determine if an individual has an ancestor belonging to a target ancestral population t generations ago based on these lengths of the ancestry-specific segments at an individual level. We applied this test on a data set that includes 20 Uruguayan admixed individuals to estimate for each one how many generations ago the most recent indigenous ancestor lived. As this method tests each individual separately, it is particularly suited to small sample sizes, such as our study or ancient genome samples

Efecto de la reducción de movilidad en la segunda ola de COVID-19.

Mientras en Uruguay estamos teniendo la primera ola de la pandemia Covid-19, en muchos países ya están sufriendo la segunda. Los riesgos de saturación del sistema sanitario llevan a muchos de estos países a tomar diferentes medidas, que incluyen desde el cierre de locales gastronómicos y suspensión de clases presenciales, a restricciones en la circulación nocturna. En este trabajo estudiamos el efecto de medidas de restricción de movilidad en la curva de contagios, para un grupo de países. Estos países fueron seleccionados de acuerdo a su similaridad con con Uruguay en diferentes parámetros: son países de entre uno y doce millones de habitantes, con un esfuerzo de testeo razonable, y que en algún momento tuvieron la epidemia controlada. Para estos países, se estudian los índices de movilidad proporcionados por Google, y un índice sobre las medidas gubernamentales recopilado por la Universidad de Oxford, además de los casos nuevos diarios por cada 100.000 habitantes. En primer lugar se observa que la movilidad reportada por Google se encuentra en relación directa con las medidas gubernamentales: a mayores niveles de medidas restrictivas la movilidad se encuentra más reducida. En segundo lugar, se analiza la influencia de la reducción de movilidad sobre la velocidad de crecimiento/decrecimiento del indicador P7 (promedio en 7 días de casos nuevos por cada 100.000 habitantes), y se muestra que niveles altos de reducción de movilidad dan lugar a un decrecimiento en el índice. Finalmente, se realizan algunas observaciones sobre la duración necesaria de las restricciones de movilidad en función del nivel del máximo del P7, así como el riesgo de levantar las medidas demasiado pronto

Indigenous ancestry and admixture in the uruguayan population

The Amerindian group known as the Charrúas inhabited Uruguay at the timing of European colonial contact. Even though they were extinguished as an ethnic group as a result of a genocide, Charrúan heritage is part of the Uruguayan identity both culturally and genetically. While mitochondrial DNA studies have shown evidence of Amerindian ancestry in living Uruguayans, here we undertake whole-genome sequencing of 10 Uruguayan individuals with self-declared Charruan heritage. We detect chromosomal segments of Amerindian ancestry supporting the presence of indigenous genetic ancestry in living descendants. Specific haplotypes were found to be enriched in “Charrúas” and rare in the rest of the Amerindian groups studied. Some of these we interpret as the result of positive selection, as we identified selection signatures and they were located mostly within genes related to the infectivity of specific viruses. Historical records describe contacts of the Charrúas with other Amerindians, such as Guaraní, and patterns of genomic similarity observed here concur with genomic similarity between these groups. Less expected, we found a high genomic similarity of the Charrúas to Diaguita from Argentinian and Chile, which could be explained by geographically proximity. Finally, by fitting admixture models of Amerindian and European ancestry for the Uruguayan population, we were able to estimate the timing of the first pulse of admixture between European and Uruguayan indigenous peoples in approximately 1658 and the second migration pulse in 1683. Both dates roughly concurring with the Franciscan missions in 1662 and the foundation of the city of Colonia in 1680 by the Spanish.ANII: FSDA_1_2017_1_14364

Selection Signatures in Worldwide Sheep Populations

The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments

Integrating single marker tests in genome scans for selection : the local score approach

International audienceThe huge amount of molecular data available nowadays can help addressing new and essential questions in evolution. Answering these questions require efficient and sound mathematical and computational models and tools. The Mathematical and Computation Evolutionary Biology meetings focus on cutting-edge methodological advances in the domain, along with their foremost applications. The theme of this year's edition will be "Methods for Integrative Evolutionary Biology: various sources of data, various scales of evolution", which includes the analysis of heterogeneous data (molecular, phenotypic, ecological...), different time scales (from recent times to the origin of life), different spatial scales (from landscape to worldwide range), the combination of phylogenetics and population genetics, multidisciplinary approaches, etc. Beyond this year’s theme, general concepts, models, methods and algorithms will be presented and discussed, just as in the previous editions of MCEB. As usual, the meeting will bring together researchers originating from various disciplines: mathematics, computer science, phylogenetics, population genetics, epidemiology, ecological modeling ... Keynote speakers will introduce a field of research and discuss their own work in this field (see below). Afternoon will be for short presentations and posters, with plenty of time for discussions. We will stop early every day, thus leaving time for other activities, such as hiking or swimming. The number of attendees will be limited to favor small group interactions

Federated Learning for Data Analytics in Education

Federated learning techniques aim to train and build machine learning models based on distributed datasets across multiple devices while avoiding data leakage. The main idea is to perform training on remote devices or isolated data centers without transferring data to centralized repositories, thus mitigating privacy risks. Data analytics in education, in particular learning analytics, is a promising scenario to apply this approach to address the legal and ethical issues related to processing sensitive data. Indeed, given the nature of the data to be studied (personal data, educational outcomes, and data concerning minors), it is essential to ensure that the conduct of these studies and the publication of the results provide the necessary guarantees to protect the privacy of the individuals involved and the protection of their data. In addition, the application of quantitative techniques based on the exploitation of data on the use of educational platforms, student performance, use of devices, etc., can account for educational problems such as the determination of user profiles, personalized learning trajectories, or early dropout indicators and alerts, among others. This paper presents the application of federated learning techniques to a well-known learning analytics problem: student dropout prediction. The experiments allow us to conclude that the proposed solutions achieve comparable results from the performance point of view with the centralized versions, avoiding the concentration of all the data in a single place for training the models

An image analysis method to quantify CFTR subcellular localization

Aberrant protein subcellular localization caused by mutation is a prominent feature of many human diseases. In Cystic Fibrosis (CF), a recessive lethal disorder that results from dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the most common mutation is a deletion of phenylalanine-508 (pF508del). Such mutation produces a misfolded protein that fails to reach the cell surface. To date, over 1900 mutations have been identified in CFTR gene, but only a minority has been analyzed at the protein level. To establish if a particular CFTR variant alters its subcellular distribution, it is necessary to quantitatively determine protein localization in the appropriate cellular context. To date, most quantitative studies on CFTR localization have been based on immunoprecipitation and western blot. In this work, we developed and validated a confocal microscopy-image analysis method to quantitatively examine CFTR at the apical membrane of epithelial cells. Polarized MDCK cells transiently transfected with EGFP-CFTR constructs and stained for an apical marker were used. EGFP-CFTR fluorescence intensity in a region defined by the apical marker was normalized to EGFP-CFTR whole cell fluorescence intensity, rendering “apical CFTR ratio”. We obtained an apical CFTR ratio of 0.67 ± 0.05 for wtCFTR and 0.11 ± 0.02 for pF508del. In addition, this image analysis method was able to discriminate intermediate phenotypes: partial rescue of the pF508del by incubation at 27 °C rendered an apical CFTR ratio value of 0.23 ± 0.01. We concluded the method has a good sensitivity and accurately detects milder phenotypes. Improving axial resolution through deconvolution further increased the sensitivity of the system as rendered an apical CFTR ratio of 0.76 ± 0.03 for wild type and 0.05 ± 0.02 for pF508del. The presented procedure is faster and simpler when compared with other available methods and it is therefore suitable as a screening method to identify mutations that completely or mildly affect CFTR processing. Moreover, it could be extended to other studies on the biology underlying protein subcellular localization in health and disease.Fil: Pizzo, Lucilla. Instituto Pasteur de Montevideo; UruguayFil: Fariello, María Inés. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Lepanto, Paola. Instituto Pasteur de Montevideo; UruguayFil: Aguilar, Pablo Sebastián. Instituto Pasteur de Montevideo; UruguayFil: Kierbel, Arlinet Verónica. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

A local score approach improves GWAS resolution and detects minor QTL: application to Medicago truncatula quantitative disease resistance to multiple Aphanomyces euteiches isolates

International audienceQuantitative trait loci (QTL) with small effects, which are pervasive in quantitative phenotypic variation, are difficult to detect in genome-wide association studies (GWAS). To improve their detection, we propose to use a local score approach that accounts for the surrounding signal due to linkage disequilibrium, by accumulating association signals from contiguous single markers. Simulations revealed that, in a GWAS context with high marker density, the local score approach outperforms single SNP p-value-based tests for detecting minor QTL (heritability of 5-10%) and is competitive with regard to alternative methods, which also aggregate p-values. Using more than five million SNPs, this approach was applied to identify loci involved in Quantitative Disease Resistance (QDR) to different isolates of the plant root rot pathogen Aphanomyces euteiches, from a GWAS performed on a collection of 174 accessions of the model legume Medicago truncatula. We refined the position of a previously reported major locus, underlying MYB/NB-ARC/tyrosine kinase candidate genes conferring resistance to two closely related A. euteiches isolates belonging to pea pathotype I. We also discovered a diversity of minor resistance QTL, not detected using p-value-based tests, some of which being putatively shared in response to pea (pathotype I and III) and/or alfalfa (race 1 and 2) isolates. Candidate genes underlying these QTL suggest pathogen effector recognition and plant proteasome as key functions associated with M. truncatula resistance to A. euteiches. GWAS on any organism can benefit from the local score approach to uncover many weak-effect QTL

Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B

Abstract Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood. Here we uncover a novel interaction between CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably, depletion of these kinesin 1 components results in abnormally elongated cilia. Furthermore, through genetic interaction studies we demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a previously unknown role of kinesin 1 in cilia length regulation that relies on the BBS related protein CCDC28B