hacksig: a unified and tidy R framework to easily compute gene expression signature scores

Carenzo, Andrea; Pistore, Federico; Serafini, Mara Serena; Lenoci, Deborah; Licata, Armando G; Cecco, Loris De

doi:10.1093/bioinformatics/btac161

Cited by 7 publications

(6 citation statements)

References 15 publications

(19 reference statements)

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“…To determine whether non-canonical module expression in untreated, non-metastatic primary tumors could serve as a biomarker of clinical outcome, we performed single sample gene set enrichment analysis (ssGSEA 44 ) on two independent datasets of pre-treatment primary tumors, the cancer genome atlas (TCGA) cohort of 445 patients with Stage I-IV colon or rectal adenocarcinoma 45, and an MSKCC cohort of 108 patients with locally advanced (Stage II-III) rectal cancers (LARC) 46 . Expression of non-canonical modules is (which was not certified by peer review) is the author/funder.…”

Section: Non-canonical Gene Expression Varies Across Patients and Is ...mentioning

confidence: 99%

Progressive plasticity during colorectal cancer metastasis

Moorman,

Cambuli,

Benitez

et al. 2023

Preprint

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Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt Lgr5+ intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

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Section: Non-canonical Gene Expression Varies Across Patients and Is ...mentioning

confidence: 99%

Progressive plasticity during colorectal cancer metastasis

Moorman,

Cambuli,

Benitez

et al. 2023

Preprint

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“…Kaplan-Meier analysis showed that low-score LARCs had significantly lower DFS than high-score LARCs ( Figures 4D, F ). In contrast, Kaplan-Meier analysis showed there was no significant difference in survival between two groups based on the median immunophenoscore (IS) ( 23 , 24 ) ( Figures 4E, G ), suggesting that the score system of immunophenoscore failed to exploit the opportunity of predicting the LARCs prognosis.…”

Section: Resultsmentioning

confidence: 90%

“…Furthermore, we investigated effects of the immune-associated configuration on patient survival by predicting the LARCs prognosis based on the IPS. Firstly, we calculated tumor purity scores (TPS) for patients in GSE3952 and GSE87211 by the R package hacksig ( 23 ). In GSE39582, the mean TPS of the high-score group was 0.338, and the low-score group was 0.388.…”

Section: Resultsmentioning

confidence: 99%

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An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer

Xue

Yang²,

Luo³

et al. 2022

Front. Oncol.

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Background and purposeAccumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.Material and methodsA novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.ResultsThe immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model’s immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.ConclusionThe immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well.

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“…Identification of fibroblast clusters was performed using principal component analysis (PCA) and hierarchical clustering using loge(1+ quantile normalized count) with the Euclidian distance used to calculate the distance matrix according to Ward's linkage 51 . Comparison to publicly available fibroblast/CAF signatures was performed by calculating combined z-scores 52 using the tidy framework hacksig 53 . Gene expression or combined z-scores were visualized using EnhancedVolcano 54 and/or pheatmap 55 .…”

Section: Rna Isolation Bulk Transcriptomics Cdna Synthesis and Quanti...mentioning

confidence: 99%

Phenotypic plasticity, spatial niches and cancer-associated fibroblast/mural cell interactions define the human prostate cancer microenvironment

Sampson,

Brunner,

Damisch

et al. 2023

Preprint

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Due to their established roles in tumor progression and therapy resistance, cancer-associated fibroblasts (CAFs) are considered key therapeutic targets. However, a lack of pre-clinical models has hampered the functional characterization of tumor-promoting versus tumor-suppressive CAF substates, a priori for the development of CAF-targeted therapeutics. We describe and cross-validate a biobank of primary human prostate inflammatory (iCAFs) and myofibroblastic (myCAFs) CAFs that closely recapitulate fibroblast heterogeneity in clinical prostate cancer (PCa) and retain key functional hallmarks pertinent to their CAF substate. iCAFs and myCAFs coexisted in clinical specimens but localized to distinct spatial niches and differentially expressed androgen receptor (AR). Pro-migratory AR-negative myCAFs retained high plasticity in a biomechanical-sensitive manner and were associated with hallmarks of poor outcome. Consistently, myCAFs represented the dominant CAF subpopulation in fibroblast-rich high-grade PCa and castration-resistant patient-derived xenografts. Conversely, AR-positive iCAFs were associated with a favorable prognosis. In view of the androgen-dependent but tumor-suppressive nature of parenchymal smooth muscle cells, these findings imply the potential inadvertent ablation of protective AR+ stromal cell types during androgen deprivation therapy may favor accumulation of aggressive AR-negative/castration-resistant myCAFs. The CAF biobank generated herein thus represents a valuable experimentally-tractable tool for the future design of CAF-targeted therapeutics to overcome therapy resistance.

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hacksig: a unified and tidy R framework to easily compute gene expression signature scores

Cited by 7 publications

References 15 publications

Progressive plasticity during colorectal cancer metastasis

Progressive plasticity during colorectal cancer metastasis

An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer

Phenotypic plasticity, spatial niches and cancer-associated fibroblast/mural cell interactions define the human prostate cancer microenvironment

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