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Complementary genomic features associated with pathway activation, gene dependency and drug sensitivity are uncovered using REVEALER.

Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.

The authors characterize a previously undescribed function of Snf5 that involves interaction with the transcription factor Gli1 and downregulation of its activity via chromatin remodeling. Snf5 is shown to restrict Hedgehog (Hh) signaling in normal development and cancer. Hh inhibition emerges as a potential therapeutic strategy for malignant rhabdoid tumors in which Snf5 is commonly lost.

GenomeSpace is an open-source, cloud-based interoperability platform that facilitates integrative genomic analyses, allowing users to transition seamlessly between a diverse and growing set of bioinformatics tools and data resources.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

The contribution of genetic factors to the tumour immune microenvironment (TIME) remains to be investigated. Here, the authors suggest the role of TIME eQTLs for target genes involved in reversing immune suppressive features.

Here, the authors use computational screening and a chemogenetic analysis of transgenic mice to show that Gα_s-coupled G-protein-coupled receptors on exhausted CD8⁺ T cells are involved in suppression of effector functions and inhibition of the protective effects of immune checkpoint immunotherapy.

Ependymoma is a tumor of the brain or spinal cord with the two most common and aggressive types mainly occurring in children. Here the authors employ 3D genomics and epigenomics to reveal targets for aggressive ependymoma tumors in children.

The role of developmental pathways in medulloblastoma tumours (MB) with sonic hedgehog (SHH) activation remains to be explored. Here, the authors perform multi-omic analysis and characterise the key transcriptomic and metabolic patterns of highly differentiated cells in SHH MBs.

Development of sensitive mass spectrometry–based assays for complex biofluids depends on the ability to identify signature peptides that produce the strongest signals. Fusaro et al. use protein physicochemical properties to predict high-responding peptides in data obtained from complex samples such as plasma.

Response rates to immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) remain low. Here the authors show that ablative treatment of tumor-draining regional lymphatics, a standard of care approach in patients, impairs the tumor response to ICI in preclinical HNSCC models.

A checklist of criteria to determine the readiness of high-throughput ‘omics’-based tests for guiding patient therapy in clinical trials is discussed; the checklist, developed by the US National Cancer Institute in collaboration with additional scientists with relevant expertise, provides a framework to evaluate the strength of evidence for a test and outlines practical issues to consider before using the test in a clinical setting, with an aim to avoid premature advancement of omics-based tests in clinical trials.

The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Medulloblastoma is the most common brain tumour in children; using exome sequencing of tumour samples the authors show that these cancers have low mutation rates and identify 12 significantly mutated genes, among them the gene encoding RNA helicase DDX3X.

The GeNets web platform can identify the most informative network, as well as execute, store and share network-based analyses of RNA-seq or genomic datasets.

Therapy-resistant cancer cell states identified across diverse contexts are selectively vulnerable to ferroptotic cell death induced by inhibition of lipid peroxidase pathways converging on GPX4.

KRAS is a proto-oncogene that is mutated in a wide variety of human cancers. Although this makes KRAS an obvious candidate for the development of targeted therapies, it has so far remained refractory to this approach. Systematic RNA interference is now used to detect synthetic lethal partners of oncogenic KRAS, revealing that TBK1 and NF-κB signalling are essential in KRAS mutant tumours. This may provide an alternative approach for targeting KRAS therapeutically.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

This protocol describes procedures for learning cellular and molecular processes from single-cell RNA-sequencing data using the non-negative matrix factorization algorithm Coordinated Gene Activity across Pattern Subsets. Parallel analysis is demonstrated in Python, R and GenePattern Notebook.

The dog is a unique model of human complex disease, and its remarkable population history makes trait mapping especially powerful. This article reviews the mapping strategies available in dogs, some key biological findings and the implications for other experimental organisms.

Medulloblastoma has been the subject of numerous genomics and transcriptomics studies that have led to this disease being subclassified into various clinically meaningful groups and to advances in understanding the biology of these subgroups, with implications for treatment.