| 1. |
- Artomov, Mykyta, et al.
(författare)
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Rare variant, gene-based association study of hereditary melanoma using whole-exome sequencing
- 2017
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 109:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM). Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by largescale joint variant calling using GATK (Genome Analysis ToolKit). PLINK/SEQ was used for statistical analysis of genetic variation. Fourmodels were used to estimate the association among different types of variants. In vitro functional validation was performed using three humanmelanoma cell lines in 2D and 3D proliferation assays. In vivo tumor growth was assessed using xenografts of humanmelanoma A375melanoma cells in nudemice (eightmice per group). All statistical tests were two-sided. Results: Strong signals were detected for CDKN2A (Pmin = 6.16×10-8) in the CM cohort (n=273) and BAP1 (Pmin = 3.83×10-6) in the OM (n=99) cohort. Eleven genes that exhibited borderline association (P < 10-4) were independently validated using The Cancer Genome Atlas melanoma cohort (379 CM, 47 OM) and a matched set of 3563 European controls with CDKN2A (P = .009), BAP1 (P = .03), and EBF3 (P = 4.75×10-4), a candidate risk locus, all showing evidence of replication. EBF3 was then evaluated using germline data from a set of 132 familial melanoma cases and 4769 controls of UK origin (joint P = 1.37×10-5). Somatically, loss of EBF3 expression correlated with progression, poorer outcome, and high MITF tumors. Functionally, induction of EBF3 in melanoma cells reduced cell growth in vitro, retarded tumor formation in vivo, and reduced MITF levels. Conclusions: The results of this large rare variant germline association study further define the mutational landscape of hereditary melanoma and implicate EBF3 as a possible CM predisposition gene.
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| 2. |
- Grüning, Björn, et al.
(författare)
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Bioconda: A sustainable and comprehensive software distribution for the life sciences
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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| 3. |
- Sundriyal, Vivek Kumar
(författare)
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Entrepreneurship as a Career : An investigation into the pre-entrepreneurship antecedents and post-entrepreneurship outcomes among the Science and Technology Labor Force (STLF) in Sweden
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation provides a career perspective on entrepreneurship based on the research question: “How do organizational bureaucracy and relative income affect the career choice of entrepreneurship among employees from the science and technology labor force (STLF); and what are the career outcomes in terms of returns during, and post entrepreneurship on re-entry into paid employment?” More specifically, the dissertation investigates (1) how mobility into entrepreneurship versus switching jobs is influenced by the level of bureaucracy in the organization and individual’s relative income compared to similar individuals and (2) how labor market returns after a period in entrepreneurship are influenced by the duration and number of prior spells in entrepreneurship, as well as the level of bureaucracy in the employer organization prior to and after entrepreneurship. Based on a matched employer-employee dataset (1990-2008) provided by Statistics Sweden, the results suggest that organizational bureaucracy and income inequality markedly influence an employee’s career choice of entrepreneurship versus a job switch, as well the initial income and entry size in entrepreneurship. Additionally, the results indicate that the returns from entrepreneurship on re-entry into paid employment differ based on the number of years in entrepreneurship, number of spells in entrepreneurship, the employer bureaucracy prior to entry into entrepreneurship, and employer bureaucracy on re-entry into paid employment. The dissertation contributes to the research on entrepreneurial careers, entrepreneurial entry, and the returns from entrepreneurship.
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