Detecting individual ancestry in the human genome

Detecting and quantifying the population substructure present in a sample of individuals are of main interest in the fields of genetic epidemiology, population genetics, and forensics among others. To date, several algorithms have been proposed for estimating the amount of genetic ancestry within an individual. In the present review, we introduce the most widely used methods in population genetics for detecting individual genetic ancestry. We further show, by means of simulations, the performance of popular algorithms for detecting individual ancestry in various controlled demographic scenarios. Finally, we provide some hints on how to interpret the results from these algorithms

GAGA: A New Algorithm for Genomic Inference of Geographic Ancestry Reveals Fine Level Population Substructure in Europeans

Attempts to detect genetic population substructure in humans are troubled by the fact that the vast majority of the total amount of observed genetic variation is present within populations rather than between populations. Here we introduce a new algorithm for transforming a genetic distance matrix that reduces the within-population variation considerably. Extensive computer simulations revealed that the transformed matrix captured the genetic population differentiation better than the original one which was based on the T1 statistic. In an empirical genomic data set comprising 2,457 individuals from 23 different European subpopulations, the proportion of individuals that were determined as a genetic neighbour to another individual from the same sampling location increased from 25% with the original matrix to 52% with the transformed matrix. Similarly, the percentage of genetic variation explained between populations by means of Analysis of Molecular Variance (AMOVA) increased from 1.62% to 7.98%. Furthermore, the first two dimensions of a classical multidimensional scaling (MDS) using the transformed matrix explained 15% of the variance, compared to 0.7% obtained with the original matrix. Application of MDS with Mclust, SPA with Mclust, and GemTools algorithms to the same dataset also showed that the transformed matrix gave a better association of the genetic clusters with the sampling locations, and particularly so when it was used in the AMOVA framework with a genetic algorithm. Overall, the new matrix transformation introduced here substantially reduces the within population genetic differentiation, and can be broadly applied to methods such as AMOVA to enhance their sensitivity to reveal population substructure. We herewith provide a publically available (http://www.erasmusmc.nl/fmb/resources/GAGA) model-free method for improved genetic population substructure detection that can be applied to human as well as any other species data in future studies relevant to evolutionary biology, behavioural ecology, medicine, and forensics

Proportioning whole-genome single-nucleotide-polymorphism diversity for the identification of geographic population structure and genetic ancestry

The identification of geographic population structure and genetic ancestry on the basis of a minimal set of genetic markers is desirable for a wide range of applications in medical and forensic sciences. However, the absence of sharp discontinuities in the neutral genetic diversity among human populations implies that, in practice, a large number of neutral markers will be required to identify the genetic ancestry of one individual. We showed that it is possible to reduce the amount of markers required for detecting continental population structure to only 10 single-nucleotide polymorphisms (SNPs), by applying a newly developed ascertainment algorithm to Affymetrix GeneChip Mapping 10K SNP array data that we obtained from samples of globally dispersed human individuals (the Y Chromosome Consortium panel). Furthermore, this set of SNPs was able to recover the genetic ancestry of individuals from all four continents represented in the original data set when applied to an independent, much larger, worldwide population data set (Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Project Cell Line Panel). Finally, we provide evidence that the unusual patterns of genetic variation we observed at the respective genomic regions surrounding the five most informative SNPs is in agreement with local positive selection being the explanation for the striking SNP allele-frequency differences we found between continental groups of human populations

Examination of non-traditional wax management techniques for flow assurance in petroleum production

Wax deposition and build-up in reservoirs, wells and pipelines negatively impact asset productivity, integrity and economics. Several flow assurance techniques have been developed to mitigate or remediate waxing problems. Prominent among these are controlling operating conditions, chemical, thermal and mechanical methods. Their major drawbacks have remained exorbitant costs over life-of-field, no single method being sufficient, risk of costly mistakes due to overdesign or underdesign, etc. Some innovative, unconventional solutions were also developed over the past 2 decades, with promising results, though mostly yet to be commercialised. This paper highlights and reflects upon these hitherto standalone technologies given the largely sparse treatise they have received in the literature. The aim is to explore alternative wax management techniques as a means of improving the science of wax deposition and dissolution. Non-traditional methods were critically examined during a 12-month extensive literature survey. In-depth study of the rationale, principle of operation, results obtained, advantages and limitations of each method was performed. Independent studies using variants of the same method were juxtaposed to ascertain similarities and differences in applicability, with meeting points established to pave the way for future research collaboration. Reflections upon their merits, limitations, areas for improvement, and a case for scale-up are presented. Some non-traditional techniques have overcome certain perennial constraints of conventional techniques widely used in industry. The wax inhibition tool, for example, has low energy requirements, causes minimal environmental impacts and has relatively low costs. The precious metals and quartz used in making the tool are available locally, the alloys were mixed in the university's materials laboratory using in-house manpower and the flow loop was locally designed and fabricated. Having developed expertise on this project through repeat and improved experiments, preparing and implementing a cost-effective work program for its commercialization is doable by the research group with industry partnership. Adapting oscillatory motion based on Avrami theory to understand mechanism and kinetics of wax crystallization by experiments on North Sea crude had yielded two opposite effects that are interesting to note. Repeat experiments a decade later using synthetic oils from Southeast Asia yielded improved results and better understanding of wax deposition kinetics; an indication that this topic holds promise to unravel some mysteries in the subject, if its deliverables are embraced and implemented. The expose provided by this paper will hopefully contribute towards available knowledge on wax management. It is expected that conscious follow up on these technologies, some of which are related and could be hybridized, would inform future research directions for both the academia and industry in the field of flow assurance

Spirometry reference equations for central European populations from school age to old age.

Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. To develop spirometry reference equations for central European populations between 8 and 90 years of age. We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings

Homeologous Plastid DNA Transformation in Tobacco Is Mediated by Multiple Recombination Events

Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance. The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced. Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA. The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers. Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA. Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids

Developement of real time diagnostics and feedback algorithms for JET in view of the next step

Real time control of many plasma parameters will be an essential aspect in the development of reliable high performance operation of Next Step Tokamaks. The main prerequisites for any feedback scheme are the precise real-time determination of the quantities to be controlled, requiring top quality and highly reliable diagnostics, and the availability of robust control algorithms. A new set of real time diagnostics was recently implemented on JET to prove the feasibility of determining, with high accuracy and time resolution, the most important plasma quantities. With regard to feedback algorithms, new model–based controllers were developed to allow a more robust control of several plasma parameters. Both diagnostics and algorithms were successfully used in several experiments, ranging from H-mode plasmas to configuration with ITBs. Since elaboration of computationally heavy measurements is often required, significant attention was devoted to non-algorithmic methods like Digital or Cellular Neural/Nonlinear Networks. The real time hardware and software adopted architectures are also described with particular attention to their relevance to ITER.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Domain-independent Extraction of Scientific Concepts from Research Articles

We examine the novel task of domain-independent scientific concept extraction from abstracts of scholarly articles and present two contributions. First, we suggest a set of generic scientific concepts that have been identified in a systematic annotation process. This set of concepts is utilised to annotate a corpus of scientific abstracts from 10 domains of Science, Technology and Medicine at the phrasal level in a joint effort with domain experts. The resulting dataset is used in a set of benchmark experiments to (a) provide baseline performance for this task, (b) examine the transferability of concepts between domains. Second, we present two deep learning systems as baselines. In particular, we propose active learning to deal with different domains in our task. The experimental results show that (1) a substantial agreement is achievable by non-experts after consultation with domain experts, (2) the baseline system achieves a fairly high F1 score, (3) active learning enables us to nearly halve the amount of required training data.Comment: Accepted for publishing in 42nd European Conference on IR Research, ECIR 202

Sulfated galactans from red seaweed Gracilaria fisheri target epidermal growth factor receptor (EGFR) and inhibit cholangiocarcinoma cells (CCA) proliferation

Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the anti-proliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, Cdk-4, Cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment