Multi-Class Cancer Subtyping in Salivary Gland Carcinomas with MALDI Imaging and Deep Learning

Simple Summary The correct diagnosis of different salivary gland carcinomas is important for a prognosis. This diagnosis is imprecise if it is based only on clinical symptoms and histological methods. Mass spectrometry imaging can provide information about the molecular composition of sample tissues. Using a deep-learning method, we analyzed the mass spectrometry imaging data of 25 patients. Using this workflow we could accurately predict the tumor type in each patient sample. Abstract Salivary gland carcinomas (SGC) are a heterogeneous group of tumors. The prognosis varies strongly according to its type, and even the distinction between benign and malign tumor is challenging. Adenoid cystic carcinoma (AdCy) is one subgroup of SGCs that is prone to late metastasis. This makes accurate tumor subtyping an important task. Matrix-assisted laser desorption/ionization (MALDI) imaging is a label-free technique capable of providing spatially resolved information about the abundance of biomolecules according to their mass-to-charge ratio. We analyzed tissue micro arrays (TMAs) of 25 patients (including six different SGC subtypes and a healthy control group of six patients) with high mass resolution MALDI imaging using a 12-Tesla magnetic resonance mass spectrometer. The high mass resolution allowed us to accurately detect single masses, with strong contributions to each class prediction. To address the added complexity created by the high mass resolution and multiple classes, we propose a deep-learning model. We showed that our deep-learning model provides a per-class classification accuracy of greater than 80% with little preprocessing. Based on this classification, we employed methods of explainable artificial intelligence (AI) to gain further insights into the spectrometric features of AdCys

Principles of Neural Network Architecture Design - Invertibility and Domain Knowledge

Neural networks architectures allow a tremendous variety of design choices. In this work, we study two principles underlying these architectures: First, the design and application of invertible neural networks (INNs). Second, the incorporation of domain knowledge into neural network architectures. After introducing the mathematical foundations of deep learning, we address the invertibility of standard feedforward neural networks from a mathematical perspective. These results serve as a motivation for our proposed invertible residual networks (i-ResNets). This architecture class is then studied in two scenarios: First, we propose ways to use i-ResNets as a normalizing flow and demonstrate the applicability for high-dimensional generative modeling. Second, we study the excessive invariance of common deep image classifiers and discuss consequences for adversarial robustness. We finish with a study of convolutional neural networks for tumor classification based on imaging mass spectrometry (IMS) data. For this application, we propose an adapted architecture guided by our knowledge of the domain of IMS data and show its superior performance on two challenging tumor classification datasets

Using probe electrospray ionization mass spectrometry and machine learning for detecting pancreatic cancer with high performance

A rapid blood-based diagnostic modality to detect pancreatic ductal adenocarcinoma (PDAC) with high accuracy is an unmet medical need. The study aimed to validate a unique diagnosis system using Probe Electrospray Ionization Mass Spectrometry (PESI-MS) and Machine Learning to the diagnosis of PDAC. Peripheral blood samples were collected from a total of 322 consecutive PDAC patients and 265 controls with a family history of PDAC. Five µl of serum samples were analyzed using PESI-MS system. The mass spectra from each specimen were then fed into machine learning algorithms to discriminate between control and cancer cases. A total of 587 serum samples were analyzed. The sensitivity of the machine learning algorithm using PESI-MS profiles to identify PDAC is 90.8% with specificity of 91.7% (95% CI 83.9%-97.4% and 82.8%-97.7% respectively). Combined PESI-MS profiles with age and CA19-9 as predictors, the accuracy for stage 1 or 2 of PDAC is 92.9% and for stage 3 or 4 is 93% (95% CI 86.3-98.2; 87.9-97.4 respectively). The accuracy and simplicity of the PESI-MS profiles combined with machine learning provide an opportunity to detect PDAC at an early stage and must be applicable to the examination of at-risk populations. [Abstract copyright: AJTR Copyright © 2020.

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

A Review on Data Fusion of Multidimensional Medical and Biomedical Data

Data fusion aims to provide a more accurate description of a sample than any one source of data alone. At the same time, data fusion minimizes the uncertainty of the results by combining data from multiple sources. Both aim to improve the characterization of samples and might improve clinical diagnosis and prognosis. In this paper, we present an overview of the advances achieved over the last decades in data fusion approaches in the context of the medical and biomedical fields. We collected approaches for interpreting multiple sources of data in different combinations: image to image, image to biomarker, spectra to image, spectra to spectra, spectra to biomarker, and others. We found that the most prevalent combination is the image-to-image fusion and that most data fusion approaches were applied together with deep learning or machine learning methods

Double Backpropagation with Applications to Robustness and Saliency Map Interpretability

This thesis is concerned with works in connection to double backpropagation, which is a phenomenon that arises when first-order optimization methods are applied to a neural network's loss function, if this contains derivatives. Its connection to robustness and saliency map interpretability is explained

Deep Learning Approaches Applied to Image Classification of Renal Tumors: A Systematic Review

Renal cancer is one of the ten most common cancers in the population that affects 65,000 new patients a year. Nowadays, to predict pathologies or classify tumors, deep learning (DL) methods are effective in addition to extracting high-performance features and dealing with segmentation tasks. This review has focused on the different studies related to the application of DL techniques for the detection or segmentation of renal tumors in patients. From the bibliographic search carried out, a total of 33 records were identified in Scopus, PubMed and Web of Science. The results derived from the systematic review give a detailed description of the research objectives, the types of images used for analysis, the data sets used, whether the database used is public or private, and the number of patients involved in the studies. The first paper where DL is applied compared to other types of tumors was in 2019 which is relatively recent. Public collection and sharing of data sets are of utmost importance to increase research in this field as many studies use private databases. We can conclude that future research will identify many benefits, such as unnecessary incisions for patients and more accurate diagnoses. As research in this field grows, the amount of open data is expected to increase.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This article is based upon work from COST Action HARMONISATION (CA20122). This research has been partially funded by the Spanish Government by the project PID2021-127275OB-I00, FEDER “Una manera de hacer Europa”

Mass spectral imaging of clinical samples using deep learning

A better interpretation of tumour heterogeneity and variability is vital for the improvement of novel diagnostic techniques and personalized cancer treatments. Tumour tissue heterogeneity is characterized by biochemical heterogeneity, which can be investigated by unsupervised metabolomics. Mass Spectrometry Imaging (MSI) combined with Machine Learning techniques have generated increasing interest as analytical and diagnostic tools for the analysis of spatial molecular patterns in tissue samples. Considering the high complexity of data produced by the application of MSI, which can consist of many thousands of spectral peaks, statistical analysis and in particular machine learning and deep learning have been investigated as novel approaches to deduce the relationships between the measured molecular patterns and the local structural and biological properties of the tissues. Machine learning have historically been divided into two main categories: Supervised and Unsupervised learning. In MSI, supervised learning methods may be used to segment tissues into histologically relevant areas e.g. the classification of tissue regions in H&E (Haemotoxylin and Eosin) stained samples. Initial classification by an expert histopathologist, through visual inspection enables the development of univariate or multivariate models, based on tissue regions that have significantly up/down-regulated ions. However, complex data may result in underdetermined models, and alternative methods that can cope with high dimensionality and noisy data are required. Here, we describe, apply, and test a novel diagnostic procedure built using a combination of MSI and deep learning with the objective of delineating and identifying biochemical differences between cancerous and non-cancerous tissue in metastatic liver cancer and epithelial ovarian cancer. The workflow investigates the robustness of single (1D) to multidimensional (3D) tumour analyses and also highlights possible biomarkers which are not accessible from classical visual analysis of the H&E images. The identification of key molecular markers may provide a deeper understanding of tumour heterogeneity and potential targets for intervention.Open Acces