| 1. |
- Ausmees, Kristiina, et al.
(författare)
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An Empirical Evaluation of Genotype Imputation of Ancient DNA
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- With capabilities of sequencing ancient DNA to high coverage often limited by sample quality or cost, imputation of missing genotypes presents a possibility to increase power of inference as well as cost-effectiveness in analysis of ancient data. However, the high degree of uncertainty often associated with ancient DNA poses several methodological challenges, and performance of imputation methods in this context has not been fully explored. To gain further insights, we performed a systematic evaluation of imputation of ancient data using BEAGLE 4.0 and reference data from phase 3 of the 1000 Genomes project, investigating the effects of coverage, phased reference and study sample size. Making use of five ancient samples with high-coverage data available, we evaluated imputed data with respect to accuracy, reference bias and genetic affinities as captured by PCA. We obtained genotype concordance levels of over 99% for data with 1x coverage, and similar levels of accuracy and reference bias at levels as low as 0.75x. Our findings suggest that using imputed data can be a realistic option for various population genetic analyses even for data in coverage ranges below 1x. We also show that a large and varied phased reference set as well as the inclusion of low- to moderate-coverage ancient samples can increase imputation performance, particularly for rare alleles. In-depth analysis of imputed data with respect to genetic variants and allele frequencies gave further insight into the nature of errors arising during imputation, and can provide practical guidelines for post-processing and validation prior to downstream analysis.
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| 2. |
- Ausmees, Kristiina
(författare)
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Efficient computational methods for applications in genomics
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last two decades, advances in molecular technology have facilitated the sequencing and analysis of ancient DNA recovered from archaeological finds, contributing to novel insights into human evolutionary history. As more ancient genetic information has become available, the need for specialized methods of analysis has also increased. In this thesis, we investigate statistical and computational models for analysis of genetic data, with a particular focus on the context of ancient DNA.The main focus is on imputation, or the inference of missing genotypes based on observed sequence data. We present results from a systematic evaluation of a common imputation pipeline on empirical ancient samples, and show that imputed data can constitute a realistic option for population-genetic analyses. We also discuss preliminary results from a simulation study comparing two methods of phasing and imputation, which suggest that the parametric Li and Stephens framework may be more robust to extremely low levels of sparsity than the parsimonious Browning and Browning model.An evaluation of methods to handle missing data in the application of PCA for dimensionality reduction of genotype data is also presented. We illustrate that non-overlapping sequence data can lead to artifacts in projected scores, and evaluate different methods for handling unobserved genotypes.In genomics, as in other fields of research, increasing sizes of data sets are placing larger demands on efficient data management and compute infrastructures. The last part of this thesis addresses the use of cloud resources for facilitating such analysis. We present two different cloud-based solutions, and exemplify them on applications from genomics.
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| 3. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 4. |
- Chylenski, Maciej, et al.
(författare)
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Late Danubian mitochondrial genomes shed light into the Neolithisation of Central Europe in the 5th millennium BC
- 2017
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Ingår i: BMC Evolutionary Biology. - : BIOMED CENTRAL LTD. - 1471-2148. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent aDNA studies are progressively focusing on various Neolithic and Hunter-Gatherer (HG) populations, providing arguments in favor of major migrations accompanying European Neolithisation. The major focus was so far on the Linear Pottery Culture (LBK), which introduced the Neolithic way of life in Central Europe in the second half of 6th millennium BC. It is widely agreed that people of this culture were genetically different from local HGs and no genetic exchange is seen between the two groups. From the other hand some degree of resurgence of HGs genetic component is seen in late Neolithic groups belonging to the complex of the Funnel Beaker Cultures (TRB). Less attention is brought to various middle Neolithic cultures belonging to Late Danubian sequence which chronologically fall in between those two abovementioned groups. We suspected that genetic influx from HG to farming communities might have happened in Late Danubian cultures since archaeologists see extensive contacts between those two communities. Results: Here we address this issue by presenting 5 complete mitochondrial genomes of various late Danubian individuals from modern-day Poland and combining it with available published data. Our data show that Late Danubian cultures are maternally closely related to Funnel Beaker groups instead of culturally similar LBK. Conclusions: We assume that it is an effect of the presence of individuals belonging to U5 haplogroup both in Late Danubians and the TRB. The U5 haplogroup is thought to be a typical for HGs of Europe and therefore we argue that it is an additional evidence of genetic exchange between farming and HG groups taking place at least as far back as in middle Neolithic, in the Late Danubian communities.
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| 5. |
- Cotgreave, Ian, et al.
(författare)
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Pyriproxifen and microcephaly: an investigation of potential ties to the ongoing "Zika epidemic"
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- As part of the Swetox mission to react to emerging concerns in chemical health and environmental safety, a preliminary litterature investigation was undertaken to gather all readily available scientific information on PPF with respect to safety assessment, in order to better understand potential links between chemical exposure and the devopment of microcephaly in affected areas. Therefore the contents of the report do not constitute an attempt at either questioning the use of existing regulatory data in the manner prescribed by international regulatory proceedures, or as a new risk assessment, based on the scientific information and concepts discussed. Here we report our findings, with particular emphasis on exisiting regulatory information, potential for lack of translation of results from regulatory animal testing to humans, lack of human exposure data and suggestions on plausible mode(s) of action of PPF in human neurodevelopmental adversities such as microcephaly.
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| 6. |
- Coutinho, Alexandra
(författare)
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Where our feet have taken us : Examples of human contact, migration, and adaptation as revealed by ancient DNA
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In spite of our extensive knowledge of the human past, certain key questions remain to be answered about human prehistory. One involves the nature of cultural change in material culture through time from the perspective of how different ancient human groups interacted with one another. The other is how humans have adapted to the different environments as they migrated and populated the rest of the world from their origin in Africa. For my thesis I have investigated examples of human evolutionary history using genetic information from ancient human remains. Chapter 1 focused on the nature of possible interaction between the Pitted Ware Culture (PWC) and Battle Axe Culture (BAC) on the island of Gotland, in the Baltic Sea. Through the analysis of 4500 year old human remains from three PWC burial sites, I found that the existence of BAC influences in these burial sites was the result of cultural and not demic influence from the BAC. In chapter 2, I investigated the ancestry of a Late Stone Age individual from the southwestern Cape of South Africa. Population genetic analyses revealed that this individual was genetically affiliated with Khoe groups in southern Africa, a genetic make-up that is today absent from the Cape. Chapter 3 investigated the genetic landscape of prehistoric individuals from southern Africa. Specifically, I explored frequencies of adaptive variants between Late Stone Age and Iron Age individuals. I found an increase in disease resistance alleles in Iron Age individuals and attributed this to the effects of the Bantu expansion. Chapter 4 incorporated a wider range of trait-associated variants among a greater number of modern-day populations and ancient individuals in Africa. I found that many allele frequency patterns found in modern populations follow the routes of major migrations which took place in the African Holocene. The thesis attests to the complexity of human demographic history in general, and how migration contributes to adaptation by dispersing novel adaptive variants to populations.
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| 7. |
- da Fonseca, Rute R., et al.
(författare)
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The origin and evolution of maize in the Southwestern United States
- 2015
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Ingår i: Nature Plants. - 2055-026X. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- The origin of maize (Zea mays mays) in the US Southwest remains contentious, with conflicting archaeological data supporting either coastal(1-4) or highland(5,6) routes of diffusion of maize into the United States. Furthermore, the genetics of adaptation to the new environmental and cultural context of the Southwest is largely uncharacterized(7). To address these issues, we compared nuclear DNA from 32 archaeological maize samples spanning 6,000 years of evolution to modern landraces. We found that the initial diffusion of maize into the Southwest about 4,000 years ago is likely to have occurred along a highland route, followed by gene flow from a lowland coastal maize beginning at least 2,000 years ago. Our population genetic analysis also enabled us to differentiate selection during domestication for adaptation to the climatic and cultural environment of the Southwest, identifying adaptation loci relevant to drought tolerance and sugar content.
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| 8. |
- Duforet-Frebourg, Nicolas, et al.
(författare)
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HaploPOP : a software that improves population assignment by combining markers into haplotypes
- 2015
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: In ecology and forensics, some population assignment techniques use molecular markers to assign individuals to known groups. However, assigning individuals to known populations can be difficult if the level of genetic differentiation among populations is small. Most assignment studies handle independent markers, often by pruning markers in Linkage Disequilibrium (LD), ignoring the information contained in the correlation among markers due to LD. Results: To improve the accuracy of population assignment, we present an algorithm, implemented in the HaploPOP software, that combines markers into haplotypes, without requiring independence. The algorithm is based on the Gain of Informativeness for Assignment that provides a measure to decide if a pair of markers should be combined into haplotypes, or not, in order to improve assignment. Because complete exploration of all possible solutions for constructing haplotypes is computationally prohibitive, our approach uses a greedy algorithm based on windows of fixed sizes. We evaluate the performance of HaploPOP to assign individuals to populations using a split-validation approach. We investigate both simulated SNPs data and dense genotype data from individuals from Spain and Portugal. Conclusions: Our results show that constructing haplotypes with HaploPOP can substantially reduce assignment error. The HaploPOP software is freely available as a command-line software at www.ieg.uu.se/Jakobsson/software/HaploPOP/.
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| 9. |
- Fraser, Magdalena, et al.
(författare)
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New insights on cultural dualism and population structure in the Middle Neolithic Funnel Beaker culture on the island of Gotland
- 2018
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 17, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- In recent years it has been shown that the Neolithization of Europe was partly driven by migration of farming groups admixing with local hunter-gatherer groups as they dispersed across the continent. However, little research has been done on the cultural duality of contemporaneous foragers and farming populations in the same region. Here we investigate the demographic history of the Funnel Beaker culture [Trichterbecherkultur or TRB, c. 4000–2800 cal BCE], and the sub-Neolithic Pitted Ware culture complex [PWC, c. 3300–2300 cal BCE] during the Nordic Middle Neolithic period on the island of Gotland, Sweden. We use a multidisciplinary approach to investigate individuals buried in the Ansarve dolmen, the only confirmed TRB burial on the island. We present new radiocarbon dating, isotopic analyses for diet and mobility, and mitochondrial DNA haplogroup data to infer maternal inheritance. We also present a new Sr-baseline of 0.71208 ± 0.0016 for the local isotope variation. We compare and discuss our findings together with that of contemporaneous populations in Sweden and the North European mainland.The radiocarbon dating and Strontium isotopic ratios show that the dolmen was used between c. 3300–2700 cal BCE by a population which displayed local Sr-signals. Mitochondrial data show that the individuals buried in the Ansarve dolmen had maternal genetic affinity to that of other Early and Middle Neolithic farming cultures in Europe, distinct from that of the contemporaneous PWC on the island. Furthermore, they exhibited a strict terrestrial and/or slightly varied diet in contrast to the strict marine diet of the PWC. The findings indicate that two different contemporary groups coexisted on the same island for several hundred years with separate cultural identity, lifestyles, as well as dietary patterns.
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| 10. |
- Fraser, Magdalena
(författare)
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People of the Dolmens and Stone Cists : An archaeogenetic Investigation of Megalithic Graves from the Neolithic Period on Gotland
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study of ancient genomics of pre-historic human remains has in recent years offered unprecedented knowledge regarding pre-historic migration and population structure on the European continent which has fundamentally altered the current views in the archaeological community. However, the merging of the two fields, archaeology and genetics, is still in its infancy and much work is still needed in order for these fields to integrate. In this thesis I explore how genetic analyses, in combination with contextual radiocarbon dating and isotopic analyses for diet and mobility can be used to investigate demographic events on a local and regional level. This is done through the investigation of people buried in five previously excavated megalithic tombs on the Island of Gotland dated to the Neolithic period. I present the genomic population structure and archaeological background for the pre-historic European reference data and show how this is used to investigate population continuity, demographic shifts, cultural duality, and admixture for local and regional contexts. I present new data and explore the Strontium-baseline for the Gotland biosphere which is used for the mobility analyses. I show that mitochondrial haplogroup data is especially useful in combination with isotopic data, and radiocarbon dating for investigation of demographic shifts on a larger scale. I also show that genomic data gives unique insights into the individuals’ life history which, together with the established demographic background allows for fine scale investigation of population demographic events within and between different archaeological contexts. Finally I show that the different Neolithic contexts on Gotland to a large extent involves immigration of new groups to the island, and that the contextual breaks seen in the archaeological record during the Neolithic period are connected with cultural and population demographic shifts. This dissertation demonstrates that genomic analyses, in combination with archaeology and isotopic analyses, as well as contextual osteological analyses and radiocarbon dating, present unique insights into the life history of the actual people who lived the lives we try to understand.
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