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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Coppejans, D. L., et al.
(författare)
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A Mildly Relativistic Outflow from the Energetic, Fast-rising Blue Optical Transient CSS161010 in a Dwarf Galaxy
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 895:1
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Tidskriftsartikel (refereegranskat)abstract
- We present X-ray and radio observations of the Fast Blue Optical Transient CRTS-CSS161010 J045834-081803 (CSS161010 hereafter) at t = 69-531 days. CSS161010 shows luminous X-ray (L-x similar to 5 x 10(39) erg s(-1)) and radio (L-nu similar to 10(29) erg s(-1) Hz(-1)) emission. The radio emission peaked at similar to 100 days post-transient explosion and rapidly decayed. We interpret these observations in the context of synchrotron emission from an expanding blast wave. CSS161010 launched a mildly relativistic outflow with velocity Gamma beta c >= 0.55c at similar to 100 days. This is faster than the non-relativistic AT 2018cow (Gamma beta c similar to 0.1c) and closer to ZTF18abvkwla (Gamma beta c >= 0.3c at 63 days). The inferred initial kinetic energy of CSS161010 (E-k greater than or similar to 10(51) erg) is comparable to that of long gamma-ray bursts, but the ejecta mass that is coupled to the mildly relativistic outflow is significantly larger (similar to 0.01-.1 M-circle dot). This is consistent with the lack of observed gamma-rays. The luminous X-rays were produced by a different emission component to the synchrotron radio emission. CSS161010 is located at similar to 150 Mpc in a dwarf galaxy with stellar mass M-* similar to 10(7) M-circle dot and specific star formation rate sSFR similar to 0.3 Gyr(-1). This mass is among the lowest inferred for host galaxies of explosive transients from massive stars. Our observations of CSS161010 are consistent with an engine-driven aspherical explosion from a rare evolutionary path of a H-rich stellar progenitor, but we cannot rule out a stellar tidal disruption event on a centrally located intermediate-mass black hole. Regardless of the physical mechanism, CSS161010 establishes the existence of a new class of rare (rate < 0.4% of the local core-collapse supernova rate) H-rich transients that can launch mildly relativistic outflows.
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- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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