scholarly journals Differential Evolution Approach to Detect Recent Admixture

2015 ◽  
Author(s):  
Konstantin Kozlov ◽  
Dmitry Chebotarov ◽  
Mehedi Hassan ◽  
Petr Triska ◽  
Martin Triska ◽  
...  
Keyword(s):  
Unmet Need ◽  
Genomic Data ◽  
Human Populations ◽  
Drug Trials ◽  
Online Tool ◽  
Multiple Origins ◽  
Mixed Origin ◽  
Evolution And Medicine ◽  
Advanced Tool ◽  
Evolution Approach

The genetic structure of human populations is extraordinarily complex and of fundamental importance to studies of anthropology, evolution, and medicine. As increasingly many individuals are of mixed origin, there is an unmet need for tools that can infer multiple origins. Misclassification of such individuals can lead to incorrect and costly misinterpretations of genomic data, primarily in disease studies and drug trials. We present an advanced tool to infer ancestry that can identify the biogeographic origins of highly mixed individuals. reAdmix can incorporate individual's knowledge of ancestors (e.g. having some ancestors from Turkey or a Scottish grandmother). reAdmix is an online tool available at http://chcb.saban-chla.usc.edu/reAdmix/.

scholarly journals COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luca Menestrina ◽  
Chiara Cabrelle ◽  
Maurizio Recanatini
Keyword(s):  
Clinical Trial ◽  
Web Application ◽  
Drug Target ◽  
Unmet Need ◽  
Target System ◽  
Holistic View ◽  
Online Tool ◽  
Clinical Drug Research ◽  
Web App ◽  
Clinical Drug

AbstractThe COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet (http://compmedchem.unibo.it/covidrugnet), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection. Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies.

scholarly journals Scaling probabilistic models of genetic variation to millions of humans

2014 ◽  
Author(s):  
Prem Gopalan ◽  
Wei Hao ◽  
David M. Blei ◽  
John D. Storey
Keyword(s):  
Population Genetics ◽  
Population Structure ◽  
Genetic Variation ◽  
Probabilistic Models ◽  
Simulated Data ◽  
Genomic Data ◽  
Human Populations ◽  
Data Sets ◽  
Complex Population ◽  
Simulated Data Sets

One of the major goals of population genetics is to quantitatively understand variation of genetic polymorphisms among individuals. To this end, researchers have developed sophisticated statistical methods to capture the complex population structure that underlies observed genotypes in humans, and such methods have been effective for analyzing modestly sized genomic data sets. However, the number of genotyped humans has grown significantly in recent years, and it is accelerating. In aggregate about 1M individuals have been genotyped to date. Analyzing these data will bring us closer to a nearly complete picture of human genetic variation; but existing methods for population genetics analysis do not scale to data of this size. To solve this problem we developed TeraStructure. TeraStructure is a new algorithm to fit Bayesian models of genetic variation in human populations on tera-sample-sized data sets (1012observed genotypes, e.g., 1M individuals at 1M SNPs). It is a principled approach to Bayesian inference that iterates between subsampling locations of the genome and updating an estimate of the latent population structure of the individuals. On data sets of up to 2K individuals, TeraStructure matches the existing state of the art in terms of both speed and accuracy. On simulated data sets of up to 10K individuals, TeraStructure is twice as fast as existing methods and has higher accuracy in recovering the latent population structure. On genomic data simulated at the tera-sample-size scales, TeraStructure continues to be accurate and is the only method that can complete its analysis.

scholarly journals Identifying loci under positive selection in complex population histories

2018 ◽  
Author(s):  
Alba Refoyo-Martínez ◽  
Rute R. da Fonseca ◽  
Katrín Halldórsdóttir ◽  
Einar Árnason ◽  
Thomas Mailund ◽  
...  
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Human Population ◽  
Genomic Data ◽  
Human Populations ◽  
Selective Sweeps ◽  
Population Genomic ◽  
Complex Population ◽  
History Of ◽  
Over Time

AbstractDetailed modeling of a species’ history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method—called Graph-aware Retrieval of Selective Sweeps (GRoSS)—has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish and human population genomic data containing multiple population panels related in complex ways. We find new candidate genes for important adaptive functions, including immunity and metabolism in under-studied human populations, as well as muscle mass, milk production and tameness in specific bovine breeds. We are also able to pinpoint the emergence of large regions of differentiation due to inversions in the history of Atlantic codfish.

scholarly journals Rapid phenotyping of knockout mice to identify genetic determinants of bone strength

2016 ◽  
Vol 231 (1) ◽  
pp. R31-R46 ◽  
Author(s):  
Bernard Freudenthal ◽  
John Logan ◽  
_ _ ◽  
Peter I Croucher ◽  
Graham R Williams ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Drug Targets ◽  
Association Studies ◽  
Unmet Need ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Genetic Determinants ◽  
Ageing Society ◽  
Skeletal Disease ◽  
And Cartilage

The genetic determinants of osteoporosis remain poorly understood, and there is a large unmet need for new treatments in our ageing society. Thus, new approaches for gene discovery in skeletal disease are required to complement the current genome-wide association studies in human populations. The International Knockout Mouse Consortium (IKMC) and the International Mouse Phenotyping Consortium (IMPC) provide such an opportunity. The IKMC generates knockout mice representing each of the known protein-coding genes in C57BL/6 mice and, as part of the IMPC initiative, the Origins of Bone and Cartilage Disease project identifies mutants with significant outlier skeletal phenotypes. This initiative will add value to data from large human cohorts and provide a new understanding of bone and cartilage pathophysiology, ultimately leading to the identification of novel drug targets for the treatment of skeletal disease.

scholarly journals Detecting Adaptive Differentiation in Structured Populations with Genomic Data and Common Gardens

Genetics ◽  
2019 ◽  
Vol 211 (3) ◽  
pp. 989-1004 ◽  
Author(s):  
Emily B. Josephs ◽  
Jeremy J. Berg ◽  
Jeffrey Ross-Ibarra ◽  
Graham Coop
Keyword(s):  
Quantitative Traits ◽  
Genomic Data ◽  
Common Garden ◽  
The United States ◽  
Structured Populations ◽  
Human Populations ◽  
United States Department ◽  
Department Of Agriculture ◽  
Common Gardens ◽  
Polygenic Adaptation

Adaptation in quantitative traits often occurs through subtle shifts in allele frequencies at many loci—a process called polygenic adaptation. While a number of methods have been developed to detect polygenic adaptation in human populations, we lack clear strategies for doing so in many other systems. In particular, there is an opportunity to develop new methods that leverage datasets with genomic data and common garden trait measurements to systematically detect the quantitative traits important for adaptation. Here, we develop methods that do just this, using principal components of the relatedness matrix to detect excess divergence consistent with polygenic adaptation, and using a conditional test to control for confounding effects due to population structure. We apply these methods to inbred maize lines from the United States Department of Agriculture germplasm pool and maize landraces from Europe. Ultimately, these methods can be applied to additional domesticated and wild species to give us a broader picture of the specific traits that contribute to adaptation and the overall importance of polygenic adaptation in shaping quantitative trait variation.

scholarly journals Сytogenetic techniques in current biomedical research. part i: history and theoretical basis of human cytogenetics

2021 ◽  
Vol 6 (4) ◽  
pp. 142-150
Author(s):  
A. N. Volkov ◽  
L. V. Nacheva
Keyword(s):  
Molecular Basis ◽  
Human Genetics ◽  
Chromosomal Abnormalities ◽  
Unmet Need ◽  
Genetic Load ◽  
Reproductive Function ◽  
Human Populations ◽  
Chromosomal Structure ◽  
Social Burden ◽  
Human Cytogenetics

Cytogenetics is an essential part of human genetics which studies the structure of chromosomes and their collection which is called karyotype. Cytogenetic techniques are employed while interrogating DNA organisation and compaction. Analysis of the chromosomal structure contributes to uncovering the molecular basis of various cellular processes in normal and pathological conditions. Furthermore, spectrum and frequency of chromosome abnormalities serves as an indicator of mutagenic effects. Cytogenetic techniques became indispensable for discovering the genetic causes of human diseases at different stages of ontogenesis. Genetic abnormalities are a common cause of impaired reproductive function, abnormal pregnancy, and neonatal malformations. Genetic screening for chromosomal abnormalities and congenital anomalies is a powerful tool for reducing the genetic load in human populations as well as disease, psychological and social burden on families and societies. This paper begins the cycle of lectures on molecular basis of human cytogenetics, cytogenetic techniques, and the corresponding research and clinical applications. The lecture is primarily aimed at biomedical students and physicians who often have an unmet need to analyse and interpret the results of cytogenetic analyses.

scholarly journals VolcanoFinder: genomic scans for adaptive introgression

2019 ◽  
Author(s):  
Derek Setter ◽  
Sylvain Mousset ◽  
Xiaoheng Cheng ◽  
Rasmus Nielsen ◽  
Michael DeGiorgio ◽  
...  
Keyword(s):  
Related Species ◽  
Genomic Data ◽  
Composite Likelihood ◽  
Genomic Variation ◽  
Human Populations ◽  
Closely Related Species ◽  
Adaptive Introgression ◽  
A Genome ◽  
Wide Range ◽  
Donor Species

AbstractRecent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method—VolcanoFinder—to detect recent events of adaptive introgression using polymorphism data from the recipient species only.VolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity.Using coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH-RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder.Author summaryThe process by which beneficial alleles are introduced into a species from a closely-related species is termed adaptive introgression. We present an analytically-tractable model for the effects of adaptive introgression on non-adaptive genetic variation in the genomic region surrounding the beneficial allele. The result we describe is a characteristic volcano-shaped pattern of increased variability that arises around the positively-selected site, and we introduce an open-source method VolcanoFinder to detect this signal in genomic data. Importantly, VolcanoFinder is a population-genetic likelihood-based approach, rather than a comparative-genomic approach, and can therefore probe genomic variation data from a single population for footprints of adaptive introgression, even from a priori unknown and possibly extinct donor species.

scholarly journals The common marmoset (Callithrix jacchus): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

2016 ◽  
Vol 3 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Bert A. 't Hart ◽  
Jordon Dunham ◽  
S. Anwar Jagessar ◽  
Yolanda S. Kap
Keyword(s):  
Animal Models ◽  
Inflammatory Disease ◽  
Clinical Success ◽  
Unmet Need ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Preclinical Model ◽  
Human Populations ◽  
Common Marmosets ◽  
New Treatments

Abstract. The increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) in aging human populations creates a high unmet need for safe and effective medications. However, thus far the translation of pathogenic concepts developed in animal models into effective treatments for the patient has been notoriously difficult. The main reason is that currently used mouse-based animal models for the pipeline selection of promising new treatments were insufficiently predictive for clinical success. Regarding the high immunological similarity between human and non-human primates (NHPs), AIMID models in NHPs can help to bridge the translational gap between rodent and man. Here we will review the preclinical relevance of the experimental autoimmune encephalomyelitis (EAE) model in common marmosets (Callithrix jacchus), a small-bodied neotropical primate. EAE is a generic AIMID model projected on the human autoimmune neuro-inflammatory disease multiple sclerosis (MS).

scholarly journals A Platform for Oncogenomic Reporting and Interpretation

2021 ◽  
Author(s):  
Caralyn Reisle ◽  
Laura Williamson ◽  
Erin Pleasance ◽  
Anna Davies ◽  
Brayden Pellegrini ◽  
...  
Keyword(s):  
Knowledge Base ◽  
Open Source ◽  
Unmet Need ◽  
Genomic Data ◽  
Molecular Data ◽  
Data Sets ◽  
Precision Oncology ◽  
Analytic Framework ◽  
Manual Curation ◽  
Rate Limiting

AbstractManual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we created the Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework created to facilitate the interpretation and reporting of somatic variants in cancer. PORI is unique in its integration of reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents one of the first open-source platform alternatives to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 TCGA tumours to the graph knowledge base, revealing that 88.2% have at least one potentially targetable alteration, and making available reports describing select individual samples.

scholarly journals Detecting adaptive differentiation in structured populations with genomic data and common gardens

2018 ◽  
Author(s):  
Emily B. Josephs ◽  
Jeremy J. Berg ◽  
Jeffrey Ross-Ibarra ◽  
Graham Coop
Keyword(s):  
Quantitative Traits ◽  
Genomic Data ◽  
Common Garden ◽  
Structured Populations ◽  
Human Populations ◽  
Trait Variation ◽  
New Methods ◽  
Common Gardens ◽  
Polygenic Adaptation ◽  
Maize Landraces

ABSTRACTAdaptation in quantitative traits often occurs through subtle shifts in allele frequencies at many loci, a process called polygenic adaptation. While a number of methods have been developed to detect polygenic adaptation in human populations, we lack clear strategies for doing so in many other systems. In particular, there is an opportunity to develop new methods that leverage datasets with genomic data and common garden trait measurements to systematically detect the quantitative traits important for adaptation. Here, we develop methods that do just this, using principal components of the relatedness matrix to detect excess divergence consistent with polygenic adaptation and using a conditional test to control for confounding effects due to population structure. We apply these methods to inbred maize lines from the USDA germplasm pool and maize landraces from Europe. Ultimately, these methods can be applied to additional domesticated and wild species to give us a broader picture of the specific traits that contribute to adaptation and the overall importance of polygenic adaptation in shaping quantitative trait variation.

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