Independent component approach to the analysis of EEG and MEG recordings

Multichannel recordings of the electromagnetic fields emerging from neural currents in the brain generate large amounts of data. Suitable feature extraction methods are, therefore, useful to facilitate the representation and interpretation of the data. Recently developed independent component analysis (ICA) has been shown to be an efficient tool for artifact identification and extraction from electroencephalographic (EEG) and magnetoen- cephalographic (MEG) recordings. In addition, ICA has been ap- plied to the analysis of brain signals evoked by sensory stimuli. This paper reviews our recent results in this field

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy.

Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins

Principal component gene set enrichment (PCGSE)

Motivation: Although principal component analysis (PCA) is widely used for the dimensional reduction of biomedical data, interpretation of PCA results remains daunting. Most existing methods attempt to explain each principal component (PC) in terms of a small number of variables by generating approximate PCs with few non-zero loadings. Although useful when just a few variables dominate the population PCs, these methods are often inadequate for characterizing the PCs of high-dimensional genomic data. For genomic data, reproducible and biologically meaningful PC interpretation requires methods based on the combined signal of functionally related sets of genes. While gene set testing methods have been widely used in supervised settings to quantify the association of groups of genes with clinical outcomes, these methods have seen only limited application for testing the enrichment of gene sets relative to sample PCs. Results: We describe a novel approach, principal component gene set enrichment (PCGSE), for computing the statistical association between gene sets and the PCs of genomic data. The PCGSE method performs a two-stage competitive gene set test using the correlation between each gene and each PC as the gene-level test statistic with flexible choice of both the gene set test statistic and the method used to compute the null distribution of the gene set statistic. Using simulated data with simulated gene sets and real gene expression data with curated gene sets, we demonstrate that biologically meaningful and computationally efficient results can be obtained from a simple parametric version of the PCGSE method that performs a correlation-adjusted two-sample t-test between the gene-level test statistics for gene set members and genes not in the set. Availability: http://cran.r-project.org/web/packages/PCGSE/index.html Contact: [email protected] or [email protected]

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

A novel R-package graphic user interface for the analysis of metabonomic profiles

Background Analysis of the plethora of metabolites found in the NMR spectra of biological fluids or tissues requires data complexity to be simplified. We present a graphical user interface (GUI) for NMR-based metabonomic analysis. The "Metabonomic Package" has been developed for metabonomics research as open-source software and uses the R statistical libraries. /Results The package offers the following options: Raw 1-dimensional spectra processing: phase, baseline correction and normalization. Importing processed spectra. Including/excluding spectral ranges, optional binning and bucketing, detection and alignment of peaks. Sorting of metabolites based on their ability to discriminate, metabolite selection, and outlier identification. Multivariate unsupervised analysis: principal components analysis (PCA). Multivariate supervised analysis: partial least squares (PLS), linear discriminant analysis (LDA), k-nearest neighbor classification. Neural networks. Visualization and overlapping of spectra. Plot values of the chemical shift position for different samples. Furthermore, the "Metabonomic" GUI includes a console to enable other kinds of analyses and to take advantage of all R statistical tools. /Conclusion We made complex multivariate analysis user-friendly for both experienced and novice users, which could help to expand the use of NMR-based metabonomics

Histopathological image analysis : a review

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe

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