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Article
Open AccessPartial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal
Hundreds of functional genomic screens have been performed across a diverse set of cancer contexts, as part of efforts such as the Cancer Dependency Map, to identify gene dependencies—genes whose loss of funct...
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Article
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias
Clinical progress in multiple myeloma (MM), an incurable plasma cell (PC) neoplasia, has been driven by therapies that have limited applications beyond MM/PC neoplasias and do not target specific oncogenic mut...
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Article
Open AccessMap** the landscape of genetic dependencies in chordoma
Identifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We apply genome-scale...
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Article
Open AccessSystematic profiling of conditional degron tag technologies for target validation studies
Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, s...
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Article
Phosphate dysregulation via the XPR1–KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer
Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR–Cas9 loss-of-function screens...
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Article
Open AccessAuthor Correction: Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells
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Article
Open AccessChronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects
CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene...
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Article
Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers
Although single-gene perturbation screens have revealed a number of new targets, vulnerabilities specific to frequently altered drivers have not been uncovered. An important question is whether the compensator...
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Article
Bridging the gap between cancer cell line models and tumours using gene expression data
Cancer cell line models are a cornerstone of cancer research, yet our understanding of how well they represent the molecular features of patient tumours remains limited. Our recent work provides a computationa...
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Article
A first-generation pediatric cancer dependency map
Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatri...
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Article
Open AccessGlobal computational alignment of tumor and cell line transcriptional profiles
Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Direct comparisons of tumor and cell line transcriptional profiles are complicate...
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Article
Open AccessMultiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action
Assays to study cancer cell responses to pharmacologic or genetic perturbations are typically restricted to using simple phenotypic readouts such as proliferation rate. Information-rich assays, such as gene-ex...
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Article
Author Correction: Cas9 activates the p53 pathway and selects for p53-inactivating mutations
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Cas9 activates the p53 pathway and selects for p53-inactivating mutations
Cas9 is commonly introduced into cell lines to enable CRISPR–Cas9-mediated genome editing. Here, we studied the genetic and transcriptional consequences of Cas9 expression itself. Gene expression profiling of ...
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Article
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Anticancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth-inhibitory activity of 4,518 drugs ...
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Article
Open AccessAgreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets
Genome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become avail...
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Article
Open AccessAuthor Correction: BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessNeuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms for its action, and ultimately for resistance, have not been fully defined. Here, usi...
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Article
Next-generation characterization of the Cancer Cell Line Encyclopedia
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets...
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Article
The landscape of cancer cell line metabolism
Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and as...
