A scale space approach for unsupervised feature selection in mass spectra classification for ovarian cancer detection

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry spectra, widely used in proteomics studies as a screening tool for protein profiling and to detect discriminatory signals, are high dimensional data. A large number of local maxima (a.k.a. <it>peaks</it>) have to be analyzed as part of computational pipelines aimed at the realization of efficient predictive and screening protocols. With this kind of data dimensions and samples size the risk of over-fitting and selection bias is pervasive. Therefore the development of bio-informatics methods based on unsupervised feature extraction can lead to general tools which can be applied to several fields of predictive proteomics.</p> <p>Results</p> <p>We propose a method for feature selection and extraction grounded on the theory of multi-scale spaces for high resolution spectra derived from analysis of serum. Then we use support vector machines for classification. In particular we use a database containing 216 samples spectra divided in 115 cancer and 91 control samples. The overall accuracy averaged over a large cross validation study is 98.18. The area under the ROC curve of the best selected model is 0.9962.</p> <p>Conclusion</p> <p>We improved previous known results on the problem on the same data, with the advantage that the proposed method has an unsupervised feature selection phase. All the developed code, as MATLAB scripts, can be downloaded from <url>http://medeaserver.isa.cnr.it/dacierno/spectracode.htm</url></p

Molecular diagnosis of cancer using ambient ionization mass spectrometry

My dissertation focuses on advancing the development and application of ambient ionization mass spectrometry methodology and technology to the biomedical field. The primary ambient ionization method used in my studies is desorption electrospray ionization mass spectrometry (DESI-MS) imaging, which has been previously used to analyze and differentiate disease state (i.e. tumor and normal) and in some cases tumor subtype of human liver, kidney, bladder, testicular, prostate, and brain cancers. DESI-MS imaging is an ideal method for disease diagnosis, because it can be used to directly correlate disease state with histopathology to develop and validate MS libraries built using the molecular profiles that relate to tissue disease states. The goal of this research is to use ambient ionization mass spectrometry for intraoperative surgical-guidance to more accurately diagnose tissue and reduce surgical times. Technological developments during the course of research revolved around touch spray ambient ionization mass spectrometry (TS-MS). This method uses a small probe (e.g. teasing needle) to pick up a minuscule amount of material from a sample, transfer the probe to the front of a mass spectrometer, and, with the addition of high voltage and solvent, induce ESI-like mechanisms for ionization. An evaluation of TS for its use as a potential in vivo surgical tool for disease screening was performed by concurrently studying prostate cancer tissue obtained from surgery with DESI-MS imaging. DESI imaging was used to first establish the relationship between MS molecular profiles and pathology which were then targeted using TS. Further, TS was also evaluated as a non-targeted technique by analyzing prostate specimens with unknown disease states and comparing the unknown data to the previously built MS targeted library. Methodological developments include DESI-MS studies for preliminary diagnosis of disease state and tumor subtyping using fine needle aspirations (FNA) of canine lymphoma specimens. Lipid profiles obtained from FNA samples were tested against a MS library built from a matched set of surgical tissue sections with disease states confirmed by histopathology. DESI-MS imaging was also used to expand upon previously investigated human kidney cancer. Previous investigations included two subtypes and low sample numbers (~10 paired normal and tumor samples per subtype), this more recent study includes the top three most commonly diagnosed subtypes (clear cell, papillary, and chromophobe) and higher sample numbers (~20 paired normal and tumor samples per subtype). In summary, many methodological and technological advances were made during the course of my dissertation studies. These advances include the development of a novel ambient ionization method, an extension of current applications to include FNA samples for early diagnosis, and an expansion of previous work to build more complex and comprehensive MS libraries. Advances such as these continue to propel ambient ionization mass spectrometry deeper into the biomedical field and gives hope to the use of chemical profiling using these methods for biomedical applications in the near future

Classification of Inflammatory Bowel Disease from Formalin‐Fixed, Paraffin‐Embedded Tissue Biopsies via Imaging Mass Spectrometry

Purpose: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact. It is therefore important to develop and improve diagnostic tools complementing traditional histomorphological approaches. Experimental Design: In this retrospective proof-of-concept study, the utilization of MALDI imaging is explored in combination with multi-variate data analysis methods to classify formalin-fixed, paraffin-embedded (FFPE) colon biopsies from UC (87 biopsies, 14 patients), CD (71 biopsies, 14 patients), and normal colonic (21 biopsies, 14 patients) tissues. Results: The proposed method results in an overall balanced accuracy of 85.7% on patient and of 80.4% on sample level, thus demonstrating that the assessment of IBD from FFPE tissue specimens via MALDI imaging is feasible. Conclusions and Clinical Relevance: The results emphasize the high potential of this method to distinguish IBD subtypes in FFPE tissue sections, which is a prerequisite for further investigations in retrospective multicenter studies, as well as for a future implementation into clinical routine

Convex non-negative matrix factorization for brain tumor delimitation from MRSI data

Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation. Methodology/Principal Findings: A pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered. Conclusions/Significance: The unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumors, which is the difficulty of appropriately delimiting the pathological area

Models and analysis of vocal emissions for biomedical applications: 5th International Workshop: December 13-15, 2007, Firenze, Italy

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies. The Workshop has the sponsorship of: Ente Cassa Risparmio di Firenze, COST Action 2103, Biomedical Signal Processing and Control Journal (Elsevier Eds.), IEEE Biomedical Engineering Soc. Special Issues of International Journals have been, and will be, published, collecting selected papers from the conference

Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites

Touch spray mass spectrometry using medical swabs is an ambient ionization technique (ionization of unprocessed sample in the open air) that has potential intraoperative application in quickly identifying the disease state of tissue and in better characterizing the resection margin. To explore this potential, we studied 29 human brain tumor specimens and obtained evidence that this technique can provide diagnostic molecular information that is relevant to brain cancer. Touch spray using medical swabs involves the physical sampling of tissue using a medical swab on a spatial scale of a few mm2 with subsequent ionization occurring directly from the swab tip upon addition of solvent and application of a high voltage. Using a tertiary mixture of acetonitrile, N,N-dimethylformamide, and ethanol, membrane-derived phospholipids and oncometabolites are extracted from the tissue, incorporated into the sprayed microdroplets, vacuumed into the mass spectrometer, and characterized in the resulting mass spectra. The tumor cell load was assessed from the complex phospholipid pattern in the mass spectra and also separately by measurement of N-acetylaspartate. Mutation status of the isocitrate dehydrogenase gene was determined via detection of the oncometabolite 2-hydroxyglutarate. The lack of sample pretreatment makes touch spray mass spectrometry using medical swabs a feasible intraoperative strategy for rapid surgical assessment

Evaluation of fractal dimension effectiveness for damage detection in retinal background

[EN] This work investigates the characterization of bright lesions in retinal fundus images using texture analysis techniques. Exudates and drusen are evidences of retinal damage in diabetic retinopathy (DR) and age-related macular degeneration (AMD) respectively. An automatic detection of pathological tissues could make possible an early detection of these diseases. In this work, fractal analysis is explored in order to discriminate between pathological and healthy retinal texture. After a deep preprocessing step, in which spatial and colour normalization are performed, the fractal dimension is extracted locally by computing the Hurst exponent (H) along different directions. The greyscale image is described by the increments of the fractional Brownian motion model and the H parameter is computed by linear regression in the frequency domain. The ability of fractal dimension to detect pathological tissues is demonstrated using a home-made system, based on fractal analysis and Support Vector Machine, able to achieve around a 70% and 83% of accuracy in E-OPHTHA and DIARETDB1 public databases respectively. In a second experiment, the fractal descriptor is combined with texture information, extracted by the Local Binary Patterns, improving the bright lesion detection. Accuracy, sensitivity and specificity values higher than 89%, 80% and 90% respectively suggest that the method presented in this paper is a robust algorithm for describing retina texture and can be useful in the automatic detection of DR and AMD.This paper was supported by the European Union's Horizon 2020 research and innovation programme under the Project GALAHAD [H2020-ICT-2016-2017, 732613]. In addition, this work was partially funded by the Ministerio de Economia y Competitividad of Spain, Project SICAP [DPI2016-77869-C2-1-R]. The work of Adrian Colomer has been supported by the Spanish Government under a FPI Grant [BES-2014-067889]. We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Titan Xp GPU used for this research.Colomer, A.; Naranjo Ornedo, V.; Janvier, T.; Mossi García, JM. (2018). Evaluation of fractal dimension effectiveness for damage detection in retinal background. Journal of Computational and Applied Mathematics. 337:341-353. https://doi.org/10.1016/j.cam.2018.01.005S34135333

Models and Analysis of Vocal Emissions for Biomedical Applications

The International Workshop on Models and Analysis of Vocal Emissions for Biomedical Applications (MAVEBA) came into being in 1999 from the particularly felt need of sharing know-how, objectives and results between areas that until then seemed quite distinct such as bioengineering, medicine and singing. MAVEBA deals with all aspects concerning the study of the human voice with applications ranging from the neonate to the adult and elderly. Over the years the initial issues have grown and spread also in other aspects of research such as occupational voice disorders, neurology, rehabilitation, image and video analysis. MAVEBA takes place every two years always in Firenze, Italy

Models and analysis of vocal emissions for biomedical applications

This book of Proceedings collects the papers presented at the 3rd International Workshop on Models and Analysis of Vocal Emissions for Biomedical Applications, MAVEBA 2003, held 10-12 December 2003, Firenze, Italy. The workshop is organised every two years, and aims to stimulate contacts between specialists active in research and industrial developments, in the area of voice analysis for biomedical applications. The scope of the Workshop includes all aspects of voice modelling and analysis, ranging from fundamental research to all kinds of biomedical applications and related established and advanced technologies