Exploration of PET and MRI radiomic features for decoding breast cancer phenotypes and prognosis.

Radiomics is an emerging technology for imaging biomarker discovery and disease-specific personalized treatment management. This paper aims to determine the benefit of using multi-modality radiomics data from PET and MR images in the characterization breast cancer phenotype and prognosis. Eighty-four features were extracted from PET and MR images of 113 breast cancer patients. Unsupervised clustering based on PET and MRI radiomic features created three subgroups. These derived subgroups were statistically significantly associated with tumor grade (p = 2.0 × 10-6), tumor overall stage (p = 0.037), breast cancer subtypes (p = 0.0085), and disease recurrence status (p = 0.0053). The PET-derived first-order statistics and gray level co-occurrence matrix (GLCM) textural features were discriminative of breast cancer tumor grade, which was confirmed by the results of L2-regularization logistic regression (with repeated nested cross-validation) with an estimated area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval (CI) = [0.62, 0.83]). The results of ElasticNet logistic regression indicated that PET and MR radiomics distinguished recurrence-free survival, with a mean AUC of 0.75 (95% CI = [0.62, 0.88]) and 0.68 (95% CI = [0.58, 0.81]) for 1 and 2 years, respectively. The MRI-derived GLCM inverse difference moment normalized (IDMN) and the PET-derived GLCM cluster prominence were among the key features in the predictive models for recurrence-free survival. In conclusion, radiomic features from PET and MR images could be helpful in deciphering breast cancer phenotypes and may have potential as imaging biomarkers for prediction of breast cancer recurrence-free survival

Cancer subtype identification pipeline: a classifusion approach

Classification of cancer patients into treatment groups is essential for appropriate diagnosis to increase survival. Previously, a series of papers, largely published in the breast cancer domain have leveraged Computational Intelligence (CI) developments and tools, resulting in ground breaking advances such as the classification of cancer into newly identified classes - leading to improved treatment options. However, the current literature on the use of CI to achieve this is fragmented, making further advances challenging. This paper captures developments in this area so far, with the goal to establish a clear, step-by-step pipeline for cancer subtype identification. Based on establishing the pipeline, the paper identifies key potential advances in CI at the individual steps, thus establishing a roadmap for future research. As such, it is the aim of the paper to engage the CI community to address the research challenges and leverage the strong potential of CI in this important area. Finally, we present a small set of recent findings on the Nottingham Tenovus Primary Breast Carcinoma Series enabling the classification of a higher number of patients into one of the identified breast cancer groups, and introduce Classifusion: a combination of results of multiple classifiers

A novel framework to elucidate core classes in a dataset

In this paper we present an original framework to extract representative groups from a dataset, and we validate it over a novel case study. The framework specifies the application of different clustering algorithms, then several statistical and visualisation techniques are used to characterise the results, and core classes are defined by consensus clustering. Classes may be verified using supervised classification algorithms to obtain a set of rules which may be useful for new data points in the future. This framework is validated over a novel set of histone markers for breast cancer patients. From a technical perspective, the resultant classes are well separated and characterised by low, medium and high levels of biological markers. Clinically, the groups appear to distinguish patients with poor overall survival from those with low grading score and better survival. Overall, this framework offers a promising methodology for elucidating core consensus groups from data

Hybrid Approach of Relation Network and Localized Graph Convolutional Filtering for Breast Cancer Subtype Classification

Network biology has been successfully used to help reveal complex mechanisms of disease, especially cancer. On the other hand, network biology requires in-depth knowledge to construct disease-specific networks, but our current knowledge is very limited even with the recent advances in human cancer biology. Deep learning has shown a great potential to address the difficult situation like this. However, deep learning technologies conventionally use grid-like structured data, thus application of deep learning technologies to the classification of human disease subtypes is yet to be explored. Recently, graph based deep learning techniques have emerged, which becomes an opportunity to leverage analyses in network biology. In this paper, we proposed a hybrid model, which integrates two key components 1) graph convolution neural network (graph CNN) and 2) relation network (RN). We utilize graph CNN as a component to learn expression patterns of cooperative gene community, and RN as a component to learn associations between learned patterns. The proposed model is applied to the PAM50 breast cancer subtype classification task, the standard breast cancer subtype classification of clinical utility. In experiments of both subtype classification and patient survival analysis, our proposed method achieved significantly better performances than existing methods. We believe that this work is an important starting point to realize the upcoming personalized medicine.Comment: 8 pages, To be published in proceeding of IJCAI 201

Relations Between Adjacency and Modularity Graph Partitioning

In this paper the exact linear relation between the leading eigenvector of the unnormalized modularity matrix and the eigenvectors of the adjacency matrix is developed. Based on this analysis a method to approximate the leading eigenvector of the modularity matrix is given, and the relative error of the approximation is derived. A complete proof of the equivalence between normalized modularity clustering and normalized adjacency clustering is also given. Some applications and experiments are given to illustrate and corroborate the points that are made in the theoretical development.Comment: 11 page

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

geneCBR: a translational tool for multiple-microarray analysis and integrative information retrieval for aiding diagnosis in cancer research

8 pages, 5 figures, 3 additional files.-- Software.[Background] Bioinformatics and medical informatics are two research fields that serve the needs of different but related communities. Both domains share the common goal of providing new algorithms, methods and technological solutions to biomedical research, and contributing to the treatment and cure of diseases. Although different microarray techniques have been successfully used to investigate useful information for cancer diagnosis at the gene expression level, the true integration of existing methods into day-to-day clinical practice is still a long way off. Within this context, case-based reasoning emerges as a suitable paradigm specially intended for the development of biomedical informatics applications and decision support systems, given the support and collaboration involved in such a translational development. With the goals of removing barriers against multi-disciplinary collaboration and facilitating the dissemination and transfer of knowledge to real practice, case-based reasoning systems have the potential to be applied to translational research mainly because their computational reasoning paradigm is similar to the way clinicians gather, analyze and process information in their own practice of clinical medicine.[Results] In addressing the issue of bridging the existing gap between biomedical researchers and clinicians who work in the domain of cancer diagnosis, prognosis and treatment, we have developed and made accessible a common interactive framework. Our geneCBR system implements a freely available software tool that allows the use of combined techniques that can be applied to gene selection, clustering, knowledge extraction and prediction for aiding diagnosis in cancer research. For biomedical researches, geneCBR expert mode offers a core workbench for designing and testing new techniques and experiments. For pathologists or oncologists, geneCBR diagnostic mode implements an effective and reliable system that can diagnose cancer subtypes based on the analysis of microarray data using a CBR architecture. For programmers, geneCBR programming mode includes an advanced edition module for run-time modification of previous coded techniques.[Conclusion] geneCBR is a new translational tool that can effectively support the integrative work of programmers, biomedical researches and clinicians working together in a common framework. The code is freely available under the GPL license and can be obtained at http://www.genecbr.org (webcite).This work is supported in part by the projects Research on Translational Bioinformatics (ref. 08VIB6) from University of Vigo and Development of computational tools for the classification and clustering of gene expression data in order to discover meaningful biological information in cancer diagnosis (ref. VA100A08) from JCyL (Spain). The work of D. Glez-Peña is supported by a "María Barbeito" contract from Xunta de Galicia.Peer reviewe

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesized that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables, can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). NPI+ was then used to predict outcome in the different molecular classes with.Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological breast cancer class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making

DERMA: A melanoma diagnosis platform based on collaborative multilabel analog reasoning

The number of melanoma cancer-related death has increased over the last few years due to the new solar habits. Early diagnosis has become the best prevention method. This work presents a melanoma diagnosis architecture based on the collaboration of several multilabel case-based reasoning subsystems called DERMA. The system has to face up several challenges that include data characterization, pattern matching, reliable diagnosis, and self-explanation capabilities. Experiments using subsystems specialized in confocal and dermoscopy images have provided promising results for helping experts to assess melanoma diagnosis