A pan-cancer atlas

A pan-cancer atlas research highlights steM CeLLs IN BRIEF What hPs Cs need GeNoMICs Yilmaz, A. et al. Nat. Cell Biol. 20, 610–619 (2018). Hoadley, K. A. et al. Cell 173, 291–304 (2018). To discover how much something is needed, it is a good strategy to try going The Cancer Genome Atlas (TCGA), a without it. Yilmaz et al. applied this program funded by the US National Institutes approach to characterize genes essential of Health (NIH), has ended over a decade for the maintenance of human pluripotent after its inception. The ambitious project stem cells (PSCs). They combined two coordinated the multi-omic sequencing and previously characterized tools: a haploid clinical annotation of approximately 10,000 human PSC line and CRISPR-based tumors across 33 cancer types. The resulting knockout screening. Along with Cas9, the resource, publicly available through the researchers delivered a library of single guide NIH Genomic Data Commons (https://gdc. RNAs (sgRNAs) targeting 18,000 genes with cancer.gov/), includes data on DNA sequence, 10 sgRNAs per gene to the cells and assessed DNA methylation, RNA and microRNA cell survival and growth rate, as well as the expression, and reverse-phase protein array abundance of sgRNAs over time. This study binding, and makes it possible to rigorously uncovered essential and growth-restricting characterize the molecular features of cancers. genes. Looking at the cellular distribution of A set of 27 analysis papers associated with the proteins encoded by the essential genes, the final data release (https://www.cell.com/ they found high proportions in nuclear and consortium/pancanceratlas) organize our mitochondrial compartments. The definition Premium current understanding by cell-of-origin of what the authors call the essentialome labware for patterns, oncogenic processes and signaling goes far beyond the known transcription pathways. A flagship paper by Hoadley et al. factors and highlights, for example, the role research and shows that tumors cluster by histology, tissue of cell-cycle regulators and DNA-repair type and anatomic origin when classified on genes in PSC growth and identity. NR discovery the basis of nearly any data type. Integrated https://doi.org/10.1038/s41592-018-0022-2 data analysis by iCluster defines various pan- cancer groupings of similar tumor types, CryoPure which will help to orient future work on MICros CoPY diagnostics and therapeutic development. TN Storage System hessian structured https://doi.org/10.1038/s41592-018-0020-4 illumination microscopy • Certified tubes, racks and Huang, X. et al. Nat. Biotechnol. 36, 451–459 (2018). boxes for cryogenic storage Neuros CIeNCe • Volumes from 1.2 to 5.0 ml analyzing Drosophila activity Structured illumination microscopy • Skirted bases and QuickSeal Cichewicz, K. & Hirsh, J. Commun. Biol. 1, 25 (2018). (SIM) offers twice the resolving power caps for ergonomic handling of diffraction-limited microscopy with Circadian rhythms, sleep and activity of relatively low doses of light compared with • 6 cap and insert colors fruit flies can be recorded in the Drosophila those required for other super-resolution for up to 36 color coding Activity Monitor (DAM) system. In this modes, which makes it useful for live options device, individual flies walk around in glass imaging. However, SIM involves image tubes with food at one end, and breaks in an reconstruction that is prone to artifacts. infrared beam that crosses the glass tube are Huang et al. have developed an approach recorded as fly activity. Several options for called Hessian-SIM to reduce artifacts in data analysis are available, but they rely on SIM image reconstruction for improved fast FREE software that requires commercial licenses or live-cell super-resolution imaging. Hessian- that might not be straightforward to install SIM uses a deconvolution algorithm based or use. Cichewicz and Hirsh developed a on Hessian matrices that makes use of a web-based solution called ShinyR-DAM, priori knowledge of an imaged structure samples! which is easy to use and can handle standard to guide image reconstruction. This experimental designs as well as multiple deconvolution algorithm outperforms genotypes and conditions. ShinyR-DAM current algorithms at low signal intensities accepts output files from the DAM system and allows imaging at a fraction of the and generates plots of individual and photon dose of conventional SIM. Using population activity, as well as summary their approach, the researchers carried graphs. A useful feature is the automated out hour-long time-lapse imaging of actin exclusion of data from dead flies. The analysis filaments in live cells and were able to image can be customized for sleep, circadian rhythm never-before-observed structures involved www.sarstedt.com or general activity studies in Drosophila. NV in endocytosis. RS customerservice@sarstedt.us https://doi.org/10.1038/s41592-018-0021-3 https://doi.org/10.1038/s41592-018-0023-1 Nature Methods | VOL 15 | JUNE 2018 | 403–409 | www.nature.com/naturemethods © 2018 Nature America Inc., part of Springer Nature. All rights reserved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Methods Springer Journals

A pan-cancer atlas

Nature Methods , Volume 15 (6) – May 31, 2018
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Publisher
Springer Journals
Copyright
Copyright © 2018 by The Author(s)
Subject
Life Sciences; Life Sciences, general; Biological Techniques; Biological Microscopy; Biomedical Engineering/Biotechnology; Bioinformatics; Proteomics
ISSN
1548-7091
eISSN
1548-7105
D.O.I.
10.1038/s41592-018-0020-4
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Abstract

research highlights steM CeLLs IN BRIEF What hPs Cs need GeNoMICs Yilmaz, A. et al. Nat. Cell Biol. 20, 610–619 (2018). Hoadley, K. A. et al. Cell 173, 291–304 (2018). To discover how much something is needed, it is a good strategy to try going The Cancer Genome Atlas (TCGA), a without it. Yilmaz et al. applied this program funded by the US National Institutes approach to characterize genes essential of Health (NIH), has ended over a decade for the maintenance of human pluripotent after its inception. The ambitious project stem cells (PSCs). They combined two coordinated the multi-omic sequencing and previously characterized tools: a haploid clinical annotation of approximately 10,000 human PSC line and CRISPR-based tumors across 33 cancer types. The resulting knockout screening. Along with Cas9, the resource, publicly available through the researchers delivered a library of single guide NIH Genomic Data Commons (https://gdc. RNAs (sgRNAs) targeting 18,000 genes with cancer.gov/), includes data on DNA sequence, 10 sgRNAs per gene to the cells and assessed DNA methylation, RNA and microRNA cell survival and growth rate, as well as the expression, and reverse-phase protein array abundance of sgRNAs over time. This study binding, and makes it possible to rigorously uncovered essential and growth-restricting characterize the molecular features of cancers. genes. Looking at the cellular distribution of A set of 27 analysis papers associated with the proteins encoded by the essential genes, the final data release (https://www.cell.com/ they found high proportions in nuclear and consortium/pancanceratlas) organize our mitochondrial compartments. The definition Premium current understanding by cell-of-origin of what the authors call the essentialome labware for patterns, oncogenic processes and signaling goes far beyond the known transcription pathways. A flagship paper by Hoadley et al. factors and highlights, for example, the role research and shows that tumors cluster by histology, tissue of cell-cycle regulators and DNA-repair type and anatomic origin when classified on genes in PSC growth and identity. NR discovery the basis of nearly any data type. Integrated https://doi.org/10.1038/s41592-018-0022-2 data analysis by iCluster defines various pan- cancer groupings of similar tumor types, CryoPure which will help to orient future work on MICros CoPY diagnostics and therapeutic development. TN Storage System hessian structured https://doi.org/10.1038/s41592-018-0020-4 illumination microscopy • Certified tubes, racks and Huang, X. et al. Nat. Biotechnol. 36, 451–459 (2018). boxes for cryogenic storage Neuros CIeNCe • Volumes from 1.2 to 5.0 ml analyzing Drosophila activity Structured illumination microscopy • Skirted bases and QuickSeal Cichewicz, K. & Hirsh, J. Commun. Biol. 1, 25 (2018). (SIM) offers twice the resolving power caps for ergonomic handling of diffraction-limited microscopy with Circadian rhythms, sleep and activity of relatively low doses of light compared with • 6 cap and insert colors fruit flies can be recorded in the Drosophila those required for other super-resolution for up to 36 color coding Activity Monitor (DAM) system. In this modes, which makes it useful for live options device, individual flies walk around in glass imaging. However, SIM involves image tubes with food at one end, and breaks in an reconstruction that is prone to artifacts. infrared beam that crosses the glass tube are Huang et al. have developed an approach recorded as fly activity. Several options for called Hessian-SIM to reduce artifacts in data analysis are available, but they rely on SIM image reconstruction for improved fast FREE software that requires commercial licenses or live-cell super-resolution imaging. Hessian- that might not be straightforward to install SIM uses a deconvolution algorithm based or use. Cichewicz and Hirsh developed a on Hessian matrices that makes use of a web-based solution called ShinyR-DAM, priori knowledge of an imaged structure samples! which is easy to use and can handle standard to guide image reconstruction. This experimental designs as well as multiple deconvolution algorithm outperforms genotypes and conditions. ShinyR-DAM current algorithms at low signal intensities accepts output files from the DAM system and allows imaging at a fraction of the and generates plots of individual and photon dose of conventional SIM. Using population activity, as well as summary their approach, the researchers carried graphs. A useful feature is the automated out hour-long time-lapse imaging of actin exclusion of data from dead flies. The analysis filaments in live cells and were able to image can be customized for sleep, circadian rhythm never-before-observed structures involved www.sarstedt.com or general activity studies in Drosophila. NV in endocytosis. RS customerservice@sarstedt.us https://doi.org/10.1038/s41592-018-0021-3 https://doi.org/10.1038/s41592-018-0023-1 Nature Methods | VOL 15 | JUNE 2018 | 403–409 | www.nature.com/naturemethods © 2018 Nature America Inc., part of Springer Nature. All rights reserved.

Journal

Nature MethodsSpringer Journals

Published: May 31, 2018

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