Shaped extensions of singular spectrum analysis

Extensions of singular spectrum analysis (SSA) for processing of non-rectangular images and time series with gaps are considered. A circular version is suggested, which allows application of the method to the data given on a circle or on a cylinder, e.g. cylindrical projection of a 3D ellipsoid. The constructed Shaped SSA method with planar or circular topology is able to produce low-rank approximations for images of complex shapes. Together with Shaped SSA, a shaped version of the subspace-based ESPRIT method for frequency estimation is developed. Examples of 2D circular SSA and 2D Shaped ESPRIT are presented

Multivariate and 2D Extensions of Singular Spectrum Analysis with the Rssa Package

Implementation of multivariate and 2D extensions of singular spectrum analysis (SSA) by means of the R package Rssa is considered. The extensions include MSSA for simultaneous analysis and forecasting of several time series and 2D-SSA for analysis of digital images. A new extension of 2D-SSA analysis called shaped 2D-SSA is introduced for analysis of images of arbitrary shape, not necessary rectangular. It is shown that implementation of shaped 2D-SSA can serve as a basis for implementation of MSSA and other generalizations. Efficient implementation of operations with Hankel and Hankel-block-Hankel matrices through the fast Fourier transform is suggested. Examples with code fragments in R, which explain the methodology and demonstrate the proper use of Rssa, are presented

Computational strategies for dissecting the high-dimensional complexity of adaptive immune repertoires

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity in order to understand the dynamics of adaptive immunity. Here, we review the current research on (i) diversity, (ii) clustering and network, (iii) phylogenetic and (iv) machine learning methods applied to dissect, quantify and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology towards coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.Comment: 27 pages, 2 figure

Shaped 3D Singular Spectrum Analysis for Quantifying Gene Expression, with Application to the Early Zebrafish Embryo

Recent progress in microscopy technologies, biological markers, and automated processing methods is making possible the development of gene expression atlases at cellular-level resolution over whole embryos. Raw data on gene expression is usually very noisy. This noise comes from both experimental (technical/methodological) and true biological sources (from stochastic biochemical processes). In addition, the cells or nuclei being imaged are irregularly arranged in 3D space. This makes the processing, extraction, and study of expression signals and intrinsic biological noise a serious challenge for 3D data, requiring new computational approaches. Here, we present a new approach for studying gene expression in nuclei located in a thick layer around a spherical surface. The method includes depth equalization on the sphere, flattening, interpolation to a regular grid, pattern extraction by Shaped 3D singular spectrum analysis (SSA), and interpolation back to original nuclear positions. The approach is demonstrated on several examples of gene expression in the zebrafish egg (a model system in vertebrate development). The method is tested on several different data geometries (e.g., nuclear positions) and different forms of gene expression patterns. Fully 3D datasets for developmental gene expression are becoming increasingly available; we discuss the prospects of applying 3D-SSA to data processing and analysis in this growing field

Assessing the Significance of Peptide Spectrum Match Scores

Peptidic Natural Products (PNPs) are highly sought after bioactive compounds that include many antibiotic, antiviral and antitumor agents, immunosuppressors and toxins. Even though recent advancements in mass-spectrometry have led to the development of accurate sequencing methods for nonlinear (cyclic and branch-cyclic) peptides, requiring only picograms of input material, the identification of PNPs via a database search of mass spectra remains problematic. This holds particularly true when trying to evaluate the statistical significance of Peptide Spectrum Matches (PSM) especially when working with non-linear peptides that often contain non-standard amino acids, modifications and have an overall complex structure. In this paper we describe a new way of estimating the statistical significance of a PSM, defined by any peptide (including linear and non-linear), by using state-of-the-art Markov Chain Monte Carlo methods. In addition to the estimate itself our method also provides an uncertainty estimate in the form of confidence bounds, as well as an automatic simulation stopping rule that ensures that the sample size is sufficient to achieve the desired level of result accuracy