| 11. |
|
|
| 12. |
- Auffray, Charles, et al.
(författare)
-
Making sense of big data in health research: Towards an EU action plan
- 2016
-
Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
-
Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
|
|
| 13. |
|
|
| 14. |
- Dyke, Stephanie O M, et al.
(författare)
-
Epigenome data release : a participant-centered approach to privacy protection
- 2015
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.
|
|
| 15. |
- Lappalainen, Tuuli, et al.
(författare)
-
Transcriptome and genome sequencing uncovers functional variation in humans
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 506-511
-
Tidskriftsartikel (refereegranskat)abstract
- Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
|
|
| 16. |
- Lindblad-Toh, Kerstin, et al.
(författare)
-
A high-resolution map of human evolutionary constraint using 29 mammals
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
-
Tidskriftsartikel (refereegranskat)abstract
- The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
|
|
| 17. |
- Pettersson, Mats, et al.
(författare)
-
A chromosome-level assembly of the Atlantic herring : detection of a supergene and other signals of selection
- 2019
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press (CSHL). - 1088-9051 .- 1549-5469. ; 29:11, s. 1919-1928
-
Tidskriftsartikel (refereegranskat)abstract
- The Atlantic herring is a model species for exploring the genetic basis for ecological adaptation, due to its huge population size and extremely low genetic differentiation at selectively neutral loci. However, such studies have so far been hampered because of a highly fragmented genome assembly. Here, we deliver a chromosome-level genome assembly based on a hybrid approach combining a de novo Pacific Biosciences (PacBio) assembly with Hi-C-supported scaffolding. The assembly comprises 26 autosomes with sizes ranging from 12.4 to 33.1 Mb and a total size, in chromosomes, of 726 Mb, which has been corroborated by a high-resolution linkage map. A comparison between the herring genome assembly with other high-quality assemblies from bony fishes revealed few inter-chromosomal but frequent intra-chromosomal rearrangements. The improved assembly facilitates analysis of previously intractable large-scale structural variation, allowing, for example, the detection of a 7.8-Mb inversion on Chromosome 12 underlying ecological adaptation. This supergene shows strong genetic differentiation between populations. The chromosome-based assembly also markedly improves the interpretation of previously detected signals of selection, allowing us to reveal hundreds of independent loci associated with ecological adaptation.
|
|
| 18. |
- Ruffier, Magali, et al.
(författare)
-
Ensembl core software resources : storage and programmatic access for DNA sequence and genome annotation
- 2017
-
Ingår i: Database. - : OXFORD UNIV PRESS. - 1758-0463.
-
Tidskriftsartikel (refereegranskat)abstract
- The Ensembl software resources are a stable infrastructure to store, access and manipulate genome assemblies and their functional annotations. The Ensembl 'Core' database and Application Programming Interface (API) was our first major piece of software infrastructure and remains at the centre of all of our genome resources. Since its initial design more than fifteen years ago, the number of publicly available genomic, transcriptomic and proteomic datasets has grown enormously, accelerated by continuous advances in DNA-sequencing technology. Initially intended to provide annotation for the reference human genome, we have extended our framework to support the genomes of all species as well as richer assembly models. Cross-referenced links to other informatics resources facilitate searching our database with a variety of popular identifiers such as UniProt and RefSeq. Our comprehensive and robust framework storing a large diversity of genome annotations in one location serves as a platform for other groups to generate and maintain their own tailored annotation. We welcome reuse and contributions: our databases and APIs are publicly available, all of our source code is released with a permissive Apache v2.0 licence at http://github.com/Ensembl and we have an active developer mailing list (http://www.ensembl.org/info/about/contact/index.html).
|
|
| 19. |
- Saunders, Gary, et al.
(författare)
-
Leveraging European infrastructures to access 1 million human genomes by 2022
- 2019
-
Ingår i: Nature reviews genetics. - : Springer Nature. - 1471-0056 .- 1471-0064. ; 20:11, s. 693-701
-
Tidskriftsartikel (refereegranskat)abstract
- Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.
|
|
| 20. |
- Uebbing, Severin, et al.
(författare)
-
Divergence in gene expression within and between two closely related flycatcher species
- 2016
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25:9, s. 2015-2028
-
Tidskriftsartikel (refereegranskat)abstract
- Relatively little is known about the character of gene expression evolution as species diverge. It is for instance unclear if gene expression generally evolves in a clock-like manner (by stabilizing selection or neutral evolution) or if there are frequent episodes of directional selection. To gain insights into the evolutionary divergence of gene expression, we sequenced and compared the transcriptomes of multiple organs from population samples of collared (Ficedula albicollis) and pied flycatchers (F. hypoleuca), two species which diverged less than one million years ago. Ordination analysis separated samples by organ rather than by species. Organs differed in their degrees of expression variance within species and expression divergence between species. Variance was negatively correlated with expression breadth and protein interactivity, suggesting that pleiotropic constraints reduce gene expression variance within species. Variance was correlated with between-species divergence, consistent with a pattern expected from stabilizing selection and neutral evolution. Using an expression PST approach, we identified genes differentially expressed between species and found 16 genes uniquely expressed in one of the species. For one of these, DPP7, uniquely expressed in collared flycatcher, the absence of expression in pied flycatcher could be associated with a ≈ 20 kb deletion including 11 out of 13 exons. This study of a young vertebrate speciation model system expands our knowledge of how gene expression evolves as natural populations become reproductively isolated.
|
|
