Defining a landscape of molecular phenotypes using a simple single sample scoring method

Foroutan, Momeneh; Bhuva, Dharmesh D.; Horan, Kristy; Lyu, Ruqian; Cursons, Joseph; Davis, Melissa J.

doi:10.1101/231217

Cited by 3 publications

(5 citation statements)

References 24 publications

(30 reference statements)

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“…The computational analysis was performed using python v3.6 together with pandas [41] for data handling, scipy [42] and numpy [43] for numerical calculations and matplotlib [44] for plotting. Gene set scoring was performed using the singscore gene set scoring approach [36].…”

Section: Computational Toolsmentioning

confidence: 99%

“…We have recently developed a gene set scoring approach [36] which uses the normalised mean rank of genes that are associated with a specific molecular phenotype or cellular behavior [32,57]. With this approach, a difference in score between two samples can be related to the percentile change in mean rank of the gene set, providing a metric which summarizes the concordance between the gene expression profile of an individual sample and the specified gene sets.…”

Section: Gene Set Scoring Allows Dimensional Reduction Of Rna-seq Datamentioning

confidence: 99%

“…Gene set scoring was performed using the singscore approach [36]. Briefly, genes are ranked by increasing transcript abundance and for a set of target genes the mean rank is calculated and normalised against theoretical minimum and maximum values.…”

Section: Gene Set Scoringmentioning

confidence: 99%

“…We have recently developed a single-sample gene set scoring method which uses a rank-based metric to quantify the relative enrichment of a gene set within a sample transcriptome [36]. We have combined NK cell signatures from the LM22/CIBERSORT [24] and LM7 [37] gene sets and curated this list to produce a gene set which reflects the relative abundance of NK cells within a tumor sample.…”

Section: Introductionmentioning

confidence: 99%

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A natural killer cell gene signature predicts melanoma patient survival

Cursons

Guimarães

Anderson

et al. 2018

Preprint

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Animal models have demonstrated that natural killer (NK) cells can limit the metastatic dissemination of tumors, however their ability to combat established human tumors has been difficult to investigate.A number of computational methods have been developed for the deconvolution of immune cell types within solid tumors. We have taken the NK cell gene signatures from several tools, then curated and expanded this list using recent reports from the literature. Using a gene set scoring method to investigate RNA-seq data from The Cancer Genome Atlas (TCGA) we show that patients with metastatic cutaneous melanoma have an improved survival rate if their tumor shows evidence of greater NK cell infiltration. Furthermore, these survival effects are enhanced in tumors which have a higher expression of NK cell stimuli such as IL-15, suggesting NK cells are part of a coordinated immune response within these patients. Using this signature we then examine transcriptomic data to identify tumor and stromal components which may influence the penetrance of NK cells into solid tumors.These data support a role for NK cells in the regulation of human tumors and highlight potential survival effects associated with increased NK cell activity. Furthermore, our computational analysis identifies a number of potential targets which may help to unleash the anti-tumor potential of NK cells as we enter the age of immunotherapy. Developmentof methodology: J. Cursons, M. Foroutan, M.J. Davis Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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Section: Computational Toolsmentioning

confidence: 99%

Section: Gene Set Scoring Allows Dimensional Reduction Of Rna-seq Datamentioning

confidence: 99%

Section: Gene Set Scoringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A natural killer cell gene signature predicts melanoma patient survival

Cursons

Guimarães

Anderson

et al. 2018

Preprint

Self Cite

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“…Studies have described the use of adsorption material, as the most significant and economical process, due to its advantages such as simplicity, regeneration ability, and optimal operation accessibility [4]. There are numerous metals, which are potentially toxic to humans and to ecology [ 7,8] but which can be used in industries for catalysis [ 9,10]. These includes nickel (Ni), manganese (Mn) chromium (Cr), palladium (Pd), zinc (Zn), etc.…”

Section: Introductionmentioning

confidence: 99%

Adsorption potentials of synthesized Mg-Al double layered hydroxide (LDH) Nanoparticles

2022

UJPICR

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Mg-Al double layered hydroxides (LDH) Nanoparticles have been synthesized using a coprecipitation method and characterized using X-ray diffraction (XRD), Scanning Electron Microscope (SEM) and Fourier Transform Infra-Red (FT-IR). The results of the XRD and SEM for the crystallite particle size of LDH-NPs (nanoparticles) were in the region of ~20 nm attributed to the smaller sized particles. The FT-IR result showed absorption bands of a possible functional group responsible for LDH formation. The adsorption analysis using Ni 2+ in aqueous solution over 3, 5 and 10 %.w/w (corresponds to 1.7x10 -3 , 2.8 x10 -3 and 5.7x10 -3 M respectively) Ni/LDH concentrations showed various degree of adsorption. Adsorption of ~95 % was achieved, which was measured using Microwave plasma Atomic emission spectroscope (MP-AES) instrument. The effect of pH and contact time showed Ni 2+ optimal adsorption on the LDH-NPs at pH 10, with equilibrium established at 30 min. The absorption capacity signifies its application in catalysis, such as for dry reforming of methane, associated with high coke formations, and in environmental application for removal of heavy metals.

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The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome

Redfern

Spalding

Thompson

2018

Clin Exp Metastasis

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Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated in the subsequent development of resistance to those same treatments. Consequently, the degree to which EMT occurs may underpin the entire course of tumour progression and treatment response in a patient. In this review we look past the protective effect of EMT against the initial treatment, to the role of the mesenchymal state, once triggered, in promoting disease growth, spread and future treatment insensitivity. In patients a correlation was found between the propensity of a treatment to induce EMT and failure of that treatment to provide a survival benefit, implicating EMT induction in accelerated tumour progression after treatment cessation. Looking to the mechanisms driving this detrimental effect; increased proliferation, suppressed apoptosis, stem cell induction, augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance, can all result from treatment-induced EMT and could worsen outcome. Evidence also suggests EMT induction with earlier therapies attenuates benefits of later treatments. Looking beyond epithelial tumours, de-differentiation also has therapy-attenuating effects and reversal thereof may yield similar rewards. A range of potential therapies are in development that may address the diverse mechanisms and molecular control systems involved in EMT-induced accelerated progression. Considering the broad reaching effects of mesenchymal shift identified, successful deployment of such treatments could substantially improve patient outcomes.

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Defining a landscape of molecular phenotypes using a simple single sample scoring method

Abstract: Background

Cited by 3 publications

References 24 publications

A natural killer cell gene signature predicts melanoma patient survival

A natural killer cell gene signature predicts melanoma patient survival

Adsorption potentials of synthesized Mg-Al double layered hydroxide (LDH) Nanoparticles

The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome

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