An Inactivating Caspase-11 Passenger Mutation Muddles Sepsis Research

Abstract Summary In the last decade, increasing attention has been paid to the study of gene fusions. However, the problem of determining whether a gene fusion is a cancer driver or just a passenger mutation is still an open issue. Here we present DEEPrior, an inherently flexible deep learning tool with two modes (Inference and Retraining). Inference mode predicts the probability of a gene fusion being involved in an oncogenic process, by directly exploiting the amino acid sequence of the fused protein. Retraining mode allows to obtain a custom prediction model including new data provided by the user. Availability and implementation Both DEEPrior and the protein fusions dataset are freely available from GitHub at (https://github.com/bioinformatics-polito/DEEPrior). The tool was designed to operate in Python 3.7, with minimal additional libraries. Supplementary information Supplementary data are available at Bioinformatics online.

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Clonal Evolution: Driver/Passenger Mutation Model in CLL

Molecular and Translational Medicine - Chronic Lymphocytic Leukemia ◽

10.1007/978-3-319-70603-0_5 ◽

2018 ◽

pp. 111-132

Author(s):

Prabhjot Kaur

Keyword(s):

Clonal Evolution ◽

Mutation Model ◽

Passenger Mutation

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A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Nature Communications ◽

10.1038/s41467-019-13825-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 13

Author(s):

Wei Jiao ◽

◽

Gurnit Atwal ◽

Paz Polak ◽

Rosa Karlic ◽

...

Keyword(s):

Deep Learning ◽

Learning System ◽

Passenger Mutation

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A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice

iScience ◽

10.1016/j.isci.2020.101870 ◽

2020 ◽

Vol 23 (12) ◽

pp. 101870

Author(s):

Marco Er-Lukowiak ◽

Yinghui Duan ◽

Francois Rassendren ◽

Lauriane Ulmann ◽

Annette Nicke ◽

...

Keyword(s):

T Cells ◽

Congenic Mice ◽

And Function ◽

Passenger Mutation

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Spontaneous Irs1 passenger mutation linked to a gene-targeted SerpinB2 allele

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1012050107 ◽

2010 ◽

Vol 107 (39) ◽

pp. 16904-16909 ◽

Cited By ~ 14

Author(s):

R. J. Westrick ◽

K. L. Mohlke ◽

L. M. Korepta ◽

A. Y. Yang ◽

G. Zhu ◽

...

Keyword(s):

Passenger Mutation

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A P2rx7 passenger mutation affects the vitality and function of immune cells in P2X4ko and other transgenic mice

10.1101/2020.06.10.139410 ◽

2020 ◽

Author(s):

Marco Er-Lukowiak ◽

Yinghui Duan ◽

Francois Rassendren ◽

Lauriane Ulmann ◽

Annette Nicke ◽

...

Keyword(s):

T Cells ◽

Transgenic Mice ◽

Immune Cell ◽

Laboratory Mouse ◽

Embryonic Stem ◽

Mouse Strains ◽

Cell Populations ◽

And Function ◽

Passenger Mutations ◽

Passenger Mutation

AbstractAmong laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 (B6) background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several 129-originating transgenic mice in which P2rx7-neighboring genes were targeted carry a P2rx7 passenger mutation that affects the vitality and function of T cells. By the example of P2rx4tm1Rass we demonstrate that CD4+ and CD8+ T cells derived from these mice express higher levels of P2X7 when compared to corresponding cell populations in B6-WT mice. The increased T cell sensitivity towards the P2X7 activators adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) rendered these cells more vulnerable towards NAD-induced cell death (NICD) compared to their B6-WT counterparts. The enhanced NICD sensitivity significantly affected the outcome of functional assays e.g. cytokine production and cell migration. For P2rx4tm1Rass, we demonstrate that the expression of P2X7 is diminished in several innate immune cell populations, possibly as a side effect of P2rx4 targeting, and independent of the P2rx7 passenger mutation. These results need to be considered when working with P2rx4tm1Rass mice or other 129-based transgenic strains that target P2rx7 neighboring genes and might have implications for other mouse models.

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Passenger mutation

The Dictionary of Genomics, Transcriptomics and Proteomics ◽

10.1002/9783527678679.dg09188 ◽

2015 ◽

pp. 1-1

Keyword(s):

Passenger Mutation

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An inactivating caspase 11 passenger mutation originating from the 129 murine strain in mice targeted for c-IAP1

Biochemical Journal ◽

10.1042/bj20120249 ◽

2012 ◽

Vol 443 (2) ◽

pp. 355-359 ◽

Cited By ~ 43

Author(s):

Niall S. Kenneth ◽

J. Michael Younger ◽

Elizabeth D. Hughes ◽

Danielle Marcotte ◽

Philip A. Barker ◽

...

Keyword(s):

Stem Cell ◽

Embryonic Stem Cell ◽

Cell Lines ◽

Target Genes ◽

Es Cells ◽

Embryonic Stem ◽

Inhibitor Of Apoptosis ◽

Stem Cell Lines ◽

Inactivating Mutation ◽

Passenger Mutation

A recent study revealed that ES (embryonic stem) cell lines derived from the 129 murine strain carry an inactivating mutation within the caspase 11 gene (Casp4) locus [Kayagaki, Warming, Lamkanfi, Vande Walle, Louie, Dong, Newton, Qu, Liu, Heldens, Zhang, Lee, Roose-Girma and Dixit (2011) Nature 479, 117–121]. Thus, if 129 ES cells are used to target genes closely linked to caspase 11, the resulting mice might also carry the caspase 11 deficiency as a passenger mutation. In the present study, we examined the genetic loci of mice targeted for the closely linked c-IAP (cellular inhibitor of apoptosis) genes, which were generated in 129 ES cells, and found that, despite extensive backcrossing into a C57BL/6 background, c-IAP1−/− animals are also deficient in caspase 11. Consequently, data obtained from these mice should be re-evaluated in this new context.

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