hist2RNA: An efficient deep learning architecture to predict gene expression from breast cancer histopathology images

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ cancer and is costly and tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n=160, corr=0.82 across patients, corr=0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n=498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index=0.56, hazard ratio=2.16, p<0.005), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index=0.65, hazard ratio=1.85, p<0.005).Comment: 15 pages, 10 figures, 2 table

Machine learning methods for histopathological image analysis

Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions.Comment: 23 pages, 4 figure

Deep Functional Mapping For Predicting Cancer Outcome

The effective understanding of the biological behavior and prognosis of cancer subtypes is becoming very important in-patient administration. Cancer is a diverse disorder in which a significant medical progression and diagnosis for each subtype can be observed and characterized. Computer-aided diagnosis for early detection and diagnosis of many kinds of diseases has evolved in the last decade. In this research, we address challenges associated with multi-organ disease diagnosis and recommend numerous models for enhanced analysis. We concentrate on evaluating the Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) for brain, lung, and breast scans to detect, segment, and classify types of cancer from biomedical images. Moreover, histopathological, and genomic classification of cancer prognosis has been considered for multi-organ disease diagnosis and biomarker recommendation. We considered multi-modal, multi-class classification during this study. We are proposing implementing deep learning techniques based on Convolutional Neural Network and Generative Adversarial Network. In our proposed research we plan to demonstrate ways to increase the performance of the disease diagnosis by focusing on a combined diagnosis of histology, image processing, and genomics. It has been observed that the combination of medical imaging and gene expression can effectively handle the cancer detection situation with a higher diagnostic rate rather than considering the individual disease diagnosis. This research puts forward a blockchain-based system that facilitates interpretations and enhancements pertaining to automated biomedical systems. In this scheme, a secured sharing of the biomedical images and gene expression has been established. To maintain the secured sharing of the biomedical contents in a distributed system or among the hospitals, a blockchain-based algorithm is considered that generates a secure sequence to identity a hash key. This adaptive feature enables the algorithm to use multiple data types and combines various biomedical images and text records. All data related to patients, including identity, pathological records are encrypted using private key cryptography based on blockchain architecture to maintain data privacy and secure sharing of the biomedical contents

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

AI-Enabled Lung Cancer Prognosis

Lung cancer is the primary cause of cancer-related mortality, claiming approximately 1.79 million lives globally in 2020, with an estimated 2.21 million new cases diagnosed within the same period. Among these, Non-Small Cell Lung Cancer (NSCLC) is the predominant subtype, characterized by a notably bleak prognosis and low overall survival rate of approximately 25% over five years across all disease stages. However, survival outcomes vary considerably based on the stage at diagnosis and the therapeutic interventions administered. Recent advancements in artificial intelligence (AI) have revolutionized the landscape of lung cancer prognosis. AI-driven methodologies, including machine learning and deep learning algorithms, have shown promise in enhancing survival prediction accuracy by efficiently analyzing complex multi-omics data and integrating diverse clinical variables. By leveraging AI techniques, clinicians can harness comprehensive prognostic insights to tailor personalized treatment strategies, ultimately improving patient outcomes in NSCLC. Overviewing AI-driven data processing can significantly help bolster the understanding and provide better directions for using such systems.Comment: This is the author's version of a book chapter entitled: "Cancer Research: An Interdisciplinary Approach", Springe

Error, reproducibility and sensitivity : a pipeline for data processing of Agilent oligonucleotide expression arrays

Background Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log2 units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells

Machine Learning of Bone Marrow Histopathology Identifies Genetic and Clinical Determinants in Patients with MDS

Publisher Copyright: ©2021 American Association for Cancer Research.In myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), bone marrow (BM) histopathology is assessed to identify dysplastic cellular morphology, cellularity, and blast excess. Yet, other morphologic findings may elude the human eye. We used convolutional neural networks to extract morphologic features from 236 MDS, 87 MDS/MPN, and 11 control BM biopsies. These features predicted genetic and cytogenetic aberrations, prognosis, age, and gender in multivariate regression models. Highest prediction accuracy was found for TET2 [area under the receiver operating curve (AUROC) = 0.94] and spliceosome mutations (0.89) and chromosome 7 monosomy (0.89). Mutation prediction probability correlated with variant allele frequency and number of affected genes per pathway, demonstrating the algorithms' ability to identify relevant morphologic patterns. By converting regression models to texture and cellular composition, we reproduced the classical del(5q) MDS morphology consisting of hypolobulated megakaryocytes. In summary, this study highlights the potential of linking deep BM histopathology with genetics and clinical variables. SIGNIFICANCE: Histopathology is elementary in the diagnostics of patients with MDS, but its high-dimensional data are underused. By elucidating the association of morphologic features with clinical variables and molecular genetics, this study highlights the vast potential of convolutional neural networks in understanding MDS pathology and how genetics is reflected in BM morphology.See related commentary by Elemento, p. 195.Peer reviewe

Altered microRNA and target gene expression related to Tetralogy of Fallot

MicroRNAs (miRNAs) play an important role in guiding development and maintaining function of the human heart. Dysregulation of miRNAs has been linked to various congenital heart diseases including Tetralogy of Fallot (TOF), which represents the most common cyanotic heart malformation in humans. Several studies have identified dysregulated miRNAs in right ventricular (RV) tissues of TOF patients. In this study, we profiled genome-wide the whole transcriptome and analyzed the relationship of miRNAs and mRNAs of RV tissues of a homogeneous group of 22 non-syndromic TOF patients. Observed profiles were compared to profiles obtained from right and left ventricular tissue of normal hearts. To reduce the commonly observed large list of predicted target genes of dysregulated miRNAs, we applied a stringent target prediction pipeline integrating probabilities for miRNA-mRNA interaction. The final list of disease-related miRNA-mRNA pairs comprises novel as well as known miRNAs including miR-1 and miR-133, which are essential to cardiac development and function by regulating KCNJ2, FBN2, SLC38A3 and TNNI1. Overall, our study provides additional insights into post-transcriptional gene regulation of malformed hearts of TOF patients