Biology subjects

Craig, S. G.

Publications and source records attributed to Craig, S. G..

3 recordsLinked to original sources

bioRxiv2021

HistoClean: Open-source Software for Histological Image Pre-processing and Augmentation to Improve Development of Robust Convolutional Neural Networks

The growth of digital pathology over the past decade has opened new research pathways and insights in cancer prediction and prognosis. In particular, there has been a surge in deep learning and computer vision techniques to analyse digital images. Common practice in this area is to use image pre-processing and augmentation to prevent bias and overfitting, creating a more robust deep learning model. Herein we introduce HistoClean; user-friendly, graphical user interface that brings together multiple image processing modules into one easy to use toolkit. In this study, we utilise HistoClean to pre-process images for a simple convolutional neural network used to detect stromal maturity, improving the accuracy of the model at a tile, region of interest, and patient level. HistoClean is free and open-source and can be downloaded from the Github repository here: https://github.com/HistoCleanQUB/HistoClean.

cancer biology↗

bioRxiv2020

The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer

STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Conversely, STING signaling can promote tumor invasion and metastasis. Currently, there is no robust method of measuring STING activation in cancer. Here, we describe an immunohistochemistry-based assay with digital pathology assessment of STING in tumor cells. Using this novel approach, we identify perinuclear-localized expression of STING (pnSTING) in estrogen receptor-positive (ER+) breast cancer as an independent predictor of good prognosis, associated with immune cell infiltration and upregulation of immune checkpoints. Tumors with low pnSTING are immunosuppressed with increased infiltration of "M2" -polarised macrophages. In ER-disease, pnSTING does not have a significant prognostic role, and STING appears to be uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression in ER+ disease is predictive of poor prognosis in independent datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.

cancer biology↗

bioRxiv2019

Chronic loss of STAG2 leads to altered chromatin structure contributing to de-regulated transcription in AML

The cohesin complex plays a major role in folding the human genome into 3D structural domains. Mutations in members of the cohesin complex are known early drivers of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), with STAG2 the most frequently mutated complex member. Here we use functional genomics to investigate the impact of chronic STAG2 loss on three-dimensional genome structure and transcriptional programming in a clinically relevant model of chronic STAG2 loss. The chronic loss of STAG2 led to loss of smaller loop domains and the maintenance/formation of large domains which in turn led to altered genome compartmentalisation. These changes in genome structure were linked with altered gene expression, including deregulation of the HOXA locus and the MAPK signalling pathway, which may contribute to disease development and response to therapy. AUTHOR SUMMARYAcute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) are clonal malignant diseases that affect the myeloid blood cell lineage. Around 40 different mutations have been identified as being associated with MDS and AML; several mutations effect genes in the cohesin complex particularly STAG2. STAG2 is an X-linked gene that is pivotal to the cohesin complex and the mutations result in a truncated gene and loss of function. We have introduced a clinically relevant truncating mutation into an isogeneic AML model. This has shown that changes in the sizes of loop and domains formed in the genome resulting in appropriate gene compartmentalisations. The associated changes in gene transcription has resulted in deregulation of HOX genes, essential for development and differentiation, and in the MAPK signalling pathway that could a therapeutic target.

cancer biology↗