| 1. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 3. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 4. |
- Angulo, Julio, 1980-, et al.
(författare)
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Understanding the user experience of secure mobile online transactions in realistic contexts of use
- 2012
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Ingår i: Symposium on Usable Privacy and Security (SOUPS) 2012. - Washington D.C.,USA : Association for Computing Machinery (ACM). ; , s. 8-
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Konferensbidrag (refereegranskat)abstract
- Possible attacks on mobile smart devices demand higher security for applications handling payments or sensitive information. The introduction of a tamper-proof area on future generations of mobile devices, called Trusted Execution Environment (TEE), is being implemented. Before devices with embedded TEEs can be deployed to the public, investigations on usability aspects of Trusted User Interfaces (TUI) are needed. This article describes the process we have followed at gathering requirements, prototyping and testing suitable designs for TUIs in combination with a touch-screen biometric system. At the end, we present relevant findings of a pilot study that we have conducted using an Experience Sampling Method (ESM) as part of our ongoing work.
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| 5. |
- Adolfsson, Emma, 1977-, et al.
(författare)
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Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death
- 2021
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 53
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Tidskriftsartikel (refereegranskat)abstract
- Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at ≥ 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.
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| 6. |
- Bergseth, Erik F., et al.
(författare)
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Extended population genetic analysis of 12 X-STRs - Exemplified using a Norwegian population sample
- 2022
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Ingår i: Forensic Science International. - : Elsevier Ireland Ltd. - 1872-4973 .- 1878-0326. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- The use of X-chromosomal markers to resolve questions of relatedness has experienced a significant increase during the last years in forensic genetics. Perhaps primarily due to the emergence of commercial kits, but equally important due to an increased awareness of the utility of those markers. The X-chromosomal inheritance pattern entails that some cases, for instance paternal half-sisters, can potentially be resolved using a few X-chromosomal markers alone. For the statistical assessment in kinship cases it is of importance to have relevant population frequency data. In the present study 631 unrelated males from a Norwegian population sample are analyzed. The resulting haplotypes are compared to previously studied population samples and a deeper analysis of the linkage disequilibrium (LD) structure is conducted. We demonstrate that the power to detect LD will be low when few males, say below 300, are analyzed. We use entropy to describe the degree of LD between multiallelic loci and describe how this measure varies between different studied populations. Large population frequency databases have been recommended when using X-chromosomal markers, and we show that by combining reference da-tabases from genetically similar populations, more precise haplotype frequency estimates can be obtained for rare haplotypes which improves the statistical assessment of the weight of evidence. In addition, we promote the use of simulations to assess the utility of STR markers in contrast to standard forensic parameters. Specifically we perform extensive simulations on cases where X-chromosomal markers are important and illustrate how the results can be used to infer the information gained from these markers.
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| 7. |
- Dorum, Guro, et al.
(författare)
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Mixtures with relatives and linked markers
- 2016
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 130:3, s. 621-634
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Tidskriftsartikel (refereegranskat)abstract
- Mixture DNA profiles commonly appear in forensic genetics, and a large number of statistical methods and software are available for such cases. However, most of the literature concerns mixtures where the contributors are assumed unrelated and the genetic markers are unlinked. In this paper, we consider mixtures of linked markers and related contributors. If no relationships are involved, linkage can be ignored. While unlinked markers can be treated independently, linkage introduces dependencies. The use of linked markers presents statistical and computational challenges, but may also lead to a considerable increase in power since the number of markers available is much larger if we do not require the markers to be unlinked. In addition, some cases that cannot be solved with an unlimited number of unlinked autosomal markers can be solved with linked markers. We focus on two special cases of linked markers: pairs of linked autosomal markers and X-chromosomal markers. A framework is presented for calculation of likelihood ratios for mixtures with general relationships and with linkage between any number of markers. Finally, we explore the effect of linkage disequilibrium, also called allelic association, on the likelihood ratio.
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| 8. |
- Egeland, Thore, et al.
(författare)
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Relationship Inference with Familias and R
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Relationship Inference in Familias and R discusses the use of Familias and R software to understand genetic kinship of two or more DNA samples. This software is commonly used for forensic cases to establish paternity, identify victims or analyze genetic evidence at crime scenes when kinship is involved. The book explores utilizing Familias software and R packages for difficult situations including inbred families, mutations and missing data from degraded DNA. The book additionally addresses identification following mass disasters, familial searching, non-autosomal marker analysis and relationship inference using linked markers. The second part of the book focuses on more statistical issues such as estimation and uncertainty of model parameters. Although written for use with human DNA, the principles can be applied to non-human genetics for animal pedigrees and/or analysis of plants for agriculture purposes. The book contains necessary tools to evaluate any type of forensic case where kinship is an issue.
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| 9. |
- Kling, Daniel, et al.
(författare)
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DNA microarray as a tool in establishing genetic relatedness-Current status and future prospects
- 2012
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 6:3, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- In the past decades, microarray technology has definitely put an edge to the field of genetic research. Our aim was to determine whether single nucleotide polymorphism (SNP) microarrays could be used as a tool in establishing genetic relationships where current molecular genetic methods are not sufficient. We used the Genechip, Affymetrix GenomeWide SNP Array 6.0, which detects more than 900,000 SNP markers dispersed throughout the human genome. The intention was to find a good selection of SNP markers that could be used for statistical evaluation of relatedness in a forensic setting. We conducted pairwise comparisons in the R-package FEST as well as pedigree comparisons in Merlin. Our methods were applied on two separate families, where relationships as distant as 3rd cousins were known. In addition, a question about a possible common ancestry between the two families was tested. Relationships as distant as 2nd cousins could be readily distinguished both from unrelated and other, genetically, closer relationships. This was achieved with a selection of 5774 markers, where each pair of markers was separated by a genetic distance of at least 0.5 cM (centiMorgan). When considering 3rd cousins, and more distant relationships, the number of markers needs to be extended, consequently decreasing the genetic distance between the markers. However, inclusion of a too large number of markers presents new challenges and our results imply that the use of too dense sets of markers always yields the highest probability for the genetically closest relationship hypothesis. Simulations confirm that this is most probably caused by the fact that the computational model assumes linkage equilibrium between markers, a problem that will be further evaluated. Our results do however suggest that SNP-data derived from microarrays are well suited for kinship determination provided linkage disequilibrium is properly accounted for.
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| 10. |
- Kling, Daniel, et al.
(författare)
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Familias 3-Extensions and new functionality
- 2014
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 13, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- In relationship testing the aim is to determine the most probable pedigree structure given genetic marker data for a set of persons. Disaster Victim Identification (DVI) based on DNA data from presumed relatives of the missing persons can be considered to be a collection of relationship problems. Forensic calculations in investigative mode address questions like "How many markers and reference persons are needed? Such questions can be answered by simulations. Mutations, deviations from Hardy-Weinberg Equilibrium (or more generally, accounting for population substructure) and silent alleles cannot be ignored when evaluating forensic evidence in case work. With the advent of new markers, so called microvariants have become more common. Previous mutation models are no longer appropriate and a new model is proposed. This paper describes methods designed to deal with DVI problems and a new simulation model to study distribution of likelihoods. There are softwares available, addressing similar problems. However, for some problems including DVI, we are not aware of freely available validated software. The Familias software has long been widely used by forensic laboratories worldwide to compute likelihoods in relationship scenarios, though previous versions have lacked desired functionality, such as the above mentioned. The extensions as well as some other novel features have been implemented in the new version, freely available at www.familias.no. The implementation and validation are briefly mentioned leaving complete details to Supplementary sections.
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