SB Driver Analysis: a Sleeping Beauty cancer driver analysis framework for identifying and prioritizing experimentally actionable oncogenes and tumor suppressors

Nucleic Acids Research
Justin Y NewbergMichael B Mann

Abstract

Cancer driver prioritization for functional analysis of potential actionable therapeutic targets is a significant challenge. Meta-analyses of mutated genes across different human cancer types for driver prioritization has reaffirmed the role of major players in cancer, including KRAS, TP53 and EGFR, but has had limited success in prioritizing genes with non-recurrent mutations in specific cancer types. Sleeping Beauty (SB) insertional mutagenesis is a powerful experimental gene discovery framework to define driver genes in mouse models of human cancers. Meta-analyses of SB datasets across multiple tumor types is a potentially informative approach to prioritize drivers, and complements efforts in human cancers. Here, we report the development of SB Driver Analysis, an in-silico method for defining cancer driver genes that positively contribute to tumor initiation and progression from population-level SB insertion data sets. We demonstrate that SB Driver Analysis computationally prioritizes drivers and defines distinct driver classes from end-stage tumors that predict their putative functions during tumorigenesis. SB Driver Analysis greatly enhances our ability to analyze, interpret and prioritize drivers from SB cancer datasets ...Continue Reading

References

Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·J A LippkeW A Haseltine
Feb 26, 2004·Nature Genetics·Stephen T ThibaultJonathan Margolis
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Jul 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Fredrik K JohanssonBengt Westermark
Sep 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sareina Chiung-Yuan WuJoseph M Kaminski
Dec 13, 2006·PLoS Computational Biology·Jeroen de RidderLodewyk Wessels
Jun 20, 2007·Nucleic Acids Research·Juan Cadiñanos, Allan Bradley
Dec 6, 2007·Genome Biology·Lara S Collier, David A Largaespada
Sep 17, 2010·Nature Reviews. Cancer·Neal G Copeland, Nancy A Jenkins
Oct 19, 2010·Nucleic Acids Research·Simon A ForbesP Andrew Futreal
Mar 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Karen M MannNeal G Copeland
Jun 16, 2012·Nature·Pedro A Pérez-ManceraDavid A Tuveson
Jan 16, 2013·Cell Reports·Ludmil B AlexandrovMichael R Stratton
Feb 22, 2013·The Journal of Investigative Dermatology·Laura M RogersAdam J Dupuy
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Sep 12, 2013·Nature Reviews. Genetics·Ian R WatsonLynda Chin
Oct 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Laura A GenovesiBrandon J Wainwright
Mar 25, 2014·Current Opinion in Genetics & Development·Michael B MannKaren M Mann
Apr 8, 2015·Nature Genetics·Michael B MannNancy A Jenkins
Jun 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Takahiro KodamaNancy A Jenkins
Nov 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Roberto RangelNeal G Copeland
Mar 24, 2017·Nucleic Acids Research·Michael A DeJesusThomas R Ioerger
Oct 24, 2017·Nucleic Acids Research·Justin Y NewbergNeal G Copeland

❮ Previous
Next ❯

Methods Mentioned

BETA
gene trap
454 sequencing

Software Mentioned

Progression Driver
SB Driver Analysis GKC
GENCODE
Ensembl
NumPy
SB Driver Analysis
Trunk Driver
splinkerette
SB Driver
Splink

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.