Abstract:
:The availability of multiple datasets comprising genome-scale RNAi viability screens in hundreds of diverse cancer cell lines presents new opportunities for understanding cancer vulnerabilities. Integrated analyses of these data to assess differential dependency across genes and cell lines are challenging due to confounding factors such as batch effects and variable screen quality, as well as difficulty assessing gene dependency on an absolute scale. To address these issues, we incorporated cell line screen-quality parameters and hierarchical Bayesian inference into DEMETER2, an analytical framework for analyzing RNAi screens ( https://depmap.org/R2-D2 ). This model substantially improves estimates of gene dependency across a range of performance measures, including identification of gold-standard essential genes and agreement with CRISPR/Cas9-based viability screens. It also allows us to integrate information across three large RNAi screening datasets, providing a unified resource representing the most extensive compilation of cancer cell line genetic dependencies to date.
journal_name
Nat Communjournal_title
Nature communicationsauthors
McFarland JM,Ho ZV,Kugener G,Dempster JM,Montgomery PG,Bryan JG,Krill-Burger JM,Green TM,Vazquez F,Boehm JS,Golub TR,Hahn WC,Root DE,Tsherniak Adoi
10.1038/s41467-018-06916-5subject
Has Abstractpub_date
2018-11-02 00:00:00pages
4610issue
1issn
2041-1723pii
10.1038/s41467-018-06916-5journal_volume
9pub_type
杂志文章abstract::SMC (structural maintenance of chromosomes) family members play essential roles in chromosome condensation, sister chromatid cohesion and DNA repair. It remains unclear how SMCs structure chromosomes and how their mechanochemical cycle regulates their interactions with DNA. Here we used single-molecule fluorescence mi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10200
更新日期:2016-01-04 00:00:00
abstract::Mutators represent a successful strategy in rapidly adapting asexual populations, but theory predicts their eventual extinction due to their unsustainably large deleterious load. While antimutator invasions have been documented experimentally, important discrepancies among studies remain currently unexplained. Here we...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11217-6
更新日期:2019-07-15 00:00:00
abstract::Third generation sequencing technologies provide the opportunity to improve genome assemblies by generating long reads spanning most repeat sequences. However, current analysis methods require substantial amounts of sequence data and computational resources to overcome the high error rates. Furthermore, they can only ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms14515
更新日期:2017-02-20 00:00:00
abstract::Intestinal intraepithelial T cells contribute to the regulation of inflammatory responses in the intestine; however, the molecular basis for their development and maintenance is unknown. The aryl hydrocarbon receptor complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and senses environmental fact...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3112
更新日期:2013-01-01 00:00:00
abstract::The bacterial effector MavC catalyzes non-canonical ubiquitination of host E2 enzyme UBE2N without engaging any of the conventional ubiquitination machinery, thereby abolishing UBE2N's function in forming K63-linked ubiquitin (Ub) chains and dampening NF-кB signaling. We now report the structures of MavC in complex wi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16587-w
更新日期:2020-06-02 00:00:00
abstract::ARID1A, a component of the SWI/SNF chromatin remodeling complex, is a tumor suppressor with a high frequency of inactivating mutations in many cancers. Therefore, ARID1A deficiency has been exploited therapeutically for treating cancer. Here we show that ARID1A has a synthetic lethal interaction with aurora kinase A (...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05694-4
更新日期:2018-08-10 00:00:00
abstract::Circadian clocks generate reliable ~24-h rhythms despite being based on stochastic biochemical reactions. The circadian clock in Synechococcus elongatus uses a post-translational oscillator that cycles deterministically in a test tube. Because the volume of a single bacterial cell is much smaller than a macroscopic re...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05109-4
更新日期:2018-08-01 00:00:00
abstract::Connection of tubules into larger networks is the key process for the development of circulatory systems. In Drosophila development, tip cells of the tracheal system lead the migration of each branch and connect tubules by adhering to each other and simultaneously changing into a torus-shape. We show that as adhesion ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11141
更新日期:2016-04-12 00:00:00
abstract::One primary reason that makes single-cell RNA-seq analysis challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Almost all computational algorithms developed for single-cell RNA-seq adopted gene selection, dimension reduction or imputation to address the dropouts. H...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14976-9
更新日期:2020-03-03 00:00:00
abstract::The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibr...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05220-6
更新日期:2018-07-24 00:00:00
abstract::Recent crystal structures of G-protein-coupled receptors (GPCRs) have revealed ordered internal water molecules, raising questions about the functional role of those waters for receptor activation that could not be answered by the static structures. Here, we used molecular dynamics simulations to monitor--at atomic an...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5733
更新日期:2014-09-09 00:00:00
abstract::FinO-domain proteins are a widespread family of bacterial RNA-binding proteins with regulatory functions. Their target spectrum ranges from a single RNA pair, in the case of plasmid-encoded FinO, to global RNA regulons, as with enterobacterial ProQ. To assess whether the FinO domain itself is intrinsically selective o...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16650-6
更新日期:2020-06-04 00:00:00
abstract::Random numbers are commonly used in many different fields, ranging from simulations in fundamental science to security applications. In some critical cases, as Bell's tests and cryptography, the random numbers are required to be both private and to be provided at an ultra-fast rate. However, practical generators are u...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07585-0
更新日期:2018-12-18 00:00:00
abstract::In the Arctic, environmental factors governing microbial degradation of soil carbon (C) in active layer and permafrost are poorly understood. Here we determined the functional potential of soil microbiomes horizontally and vertically across a cryoperturbed polygonal landscape in Alaska. With comparative metagenomics, ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03089-z
更新日期:2018-02-22 00:00:00
abstract::Large-scale genetic and genomic data are increasingly available and the major bottleneck in their analysis is a lack of sufficiently scalable computational tools. To address this problem in the context of complex traits analysis, we present DISSECT. DISSECT is a new and freely available software that is able to exploi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10162
更新日期:2015-12-11 00:00:00
abstract::Synthetic DNA is becoming an attractive substrate for digital data storage due to its density, durability, and relevance in biological research. A major challenge in making DNA data storage a reality is that reading DNA back into data using sequencing by synthesis remains a laborious, slow and expensive process. Here,...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10978-4
更新日期:2019-07-03 00:00:00
abstract::A primary function of the midbrain stimulus selection network is to compute the highest-priority location for attention and gaze. Here we report the contribution of a specific cholinergic circuit to this computation. We functionally disconnected the tegmental cholinergic nucleus isthmi pars parvocellularis (Ipc) from ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13472
更新日期:2016-11-17 00:00:00
abstract::In the original version of this Article, the legend in the upper panel of Figure 2 incorrectly read 'paternal imprinting' and should have read 'maternal imprinting'. This has been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Nature communications
pub_type: 已发布勘误
doi:10.1038/s41467-019-10155-7
更新日期:2019-05-01 00:00:00
abstract::The gravitational collapse of eruption columns generates ground-hugging pyroclastic density currents (PDCs) with highly variable temperatures, high enough to be a threat for communities surrounding volcanoes. The reasons for such great temperature variability are debated in terms of eruptive versus transport and empla...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10337-3
更新日期:2019-06-06 00:00:00
abstract::Explosive energy release is a common phenomenon occurring in magnetized plasma systems ranging from laboratories, Earth's magnetosphere, the solar corona and astrophysical environments. Its physical explanation is usually attributed to magnetic reconnection in a thin current sheet. Here we report the important role of...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1753
更新日期:2012-03-20 00:00:00
abstract::Perovskite light emitting diodes suffer from poor operational stability, exhibiting a rapid decay of external quantum efficiency within minutes to hours after turn-on. To address this issue, we explore surface treatment of perovskite films with phenylalkylammonium iodide molecules of varying alkyl chain lengths. Combi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-021-20970-6
更新日期:2021-01-28 00:00:00
abstract::Primitive carbonaceous chondrites contain a large array of organic compounds dominated by insoluble organic matter (IOM). A striking feature of this IOM is the systematic enrichment in deuterium compared with the solar hydrogen reservoir. This enrichment has been taken as a sign of low-temperature ion-molecule or gas-...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9567
更新日期:2015-10-13 00:00:00
abstract::Protein function and dynamics are closely related; however, accurate dynamics information is difficult to obtain. Here based on a carefully assembled data set derived from experimental data for proteins in solution, we quantify backbone dynamics properties on the amino-acid level and develop DynaMine--a fast, high-qua...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3741
更新日期:2013-01-01 00:00:00
abstract::Ecosystems are composed of complex networks of many species interacting in different ways. While ecologists have long studied food webs of feeding interactions, recent studies increasingly focus on mutualistic networks including plants that exchange food for reproductive services provided by animals such as pollinator...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15688-w
更新日期:2020-05-01 00:00:00
abstract::Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients,...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03750-7
更新日期:2018-05-01 00:00:00
abstract::The host-guest recognition between two macrocycles to form hierarchical non-intertwined ring-in-ring assemblies remains an interesting and challenging target in noncovalent synthesis. Herein, we report the design and characterization of a box-in-box assembly on the basis of host-guest radical-pairing interactions betw...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07673-1
更新日期:2018-12-10 00:00:00
abstract::Despite progress in understanding pollination network structure, the functional roles of floral sensory stimuli (visual, olfactory) have never been addressed comprehensively in a community context, even though such traits are known to mediate plant-pollinator interactions. Here, we use a comprehensive dataset of flora...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03448-w
更新日期:2018-03-12 00:00:00
abstract::The Aharonov-Bohm effect is one of the most intriguing phenomena in both classical and quantum physics, and associates with a number of important and fundamental issues in quantum mechanics. The Aharonov-Bohm effects of charged particles have been experimentally demonstrated and found applications in various fields. R...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4225
更新日期:2014-01-01 00:00:00
abstract::Nanoporous frameworks are polymeric materials built from rigid molecules, which give rise to their nanoporous structures with applications in gas sorption and storage, catalysis and others. Conceptually new applications could emerge, should these beneficial properties be manipulated by external stimuli in a reversible...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4588
更新日期:2014-04-07 00:00:00
abstract::Visualization and exploration of high-dimensional data is a ubiquitous challenge across disciplines. Widely used techniques such as principal component analysis (PCA) aim to identify dominant trends in one dataset. However, in many settings we have datasets collected under different conditions, e.g., a treatment and a...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04608-8
更新日期:2018-05-30 00:00:00