In this letter, we present a new method for integration of sensor-based multifrequency bands of electroencephalography and magnetoencephalography data sets into a voxel-based structural-temporal magnetic resonance imaging analysis by utilizing the general joint estimation using entropy regularization (JESTER) framework. This allows enhancement of the spatial-temporal localization of brain function and the ability to relate it to morphological features and structural connectivity. This method has broad implications for both basic neuroscience research and clinical neuroscience focused on identifying disease-relevant biomarkers by enhancing the spatial-temporal resolution of the estimates derived from current neuroimaging modalities, thereby providing a better picture of the normal human brain in basic neuroimaging experiments and variations associated with disease states.

A primary goal of many neuroimaging studies that use magnetic resonance imaging (MRI) is to deduce the structure-function relationships in the human brain using data from the three major neuro-MRI modalities: high-resolution anatomical, diffusion tensor imaging, and functional MRI. To date, the general procedure for analyzing these data is to combine the results derived independently from each of these modalities. In this article, we develop a new theoretical and computational approach for combining these different MRI modalities into a powerful and versatile framework that combines our recently developed methods for morphological shape analysis and segmentation, simultaneous local diffusion estimation and global tractography, and nonlinear and nongaussian spatial-temporal activation pattern classification and ranking, as well as our fast and accurate approach for nonlinear registration between modalities. This joint analysis method is capable of extracting new levels of information that is not achievable from any of those single modalities alone. A theoretical probabilistic framework based on a reformulation of prior information and available interdependencies between modalities through a joint coupling matrix and an efficient computational implementation allows construction of quantitative functional, structural, and effective brain connectivity modes and parcellation. This new method provides an overall increase of resolution, accuracy, level of detail, and information content and has the potential to be instrumental in the clinical adaptation of neuro-MRI modalities, which, when jointly analyzed, provide a more comprehensive view of a subject's structure-function relations, while the current standard, wherein single-modality methods are analyzed separately, leaves a critical gap in an integrated view of a subject's neuorphysiological state. As one example of this increased sensitivity, we demonstrate that the jointly estimated structural and functional dependencies of mode power follow the same power law decay with the same exponent.

The ability of functional magnetic resonance imaging (FMRI) to noninvasively measure fluctuations in brain activity in the absence of an applied stimulus offers the possibility of discerning functional networks in the resting state of the brain. However, the reconstruction of brain networks from these signal fluctuations poses a significant challenge because they are generally nonlinear and nongaussian and can overlap in both their spatial and temporal extent. Moreover, because there is no explicit input stimulus, there is no signal model with which to compare the brain responses. A variety of techniques have been devised to address this problem, but the predominant approaches are based on the presupposition of statistical properties of complex brain signal parameters, which are unprovable but facilitate the analysis. In this article, we address this problem with a new method, entropy field decomposition, for estimating structure within spatiotemporal data. This method is based on a general information field-theoretic formulation of Bayesian probability theory incorporating prior coupling information that allows the enumeration of the most probable parameter configurations without the need for unjustified statistical assumptions. This approach facilitates the construction of brain activation modes directly from the spatial-temporal correlation structure of the data. These modes and their associated spatial-temporal correlation structure can then be used to generate space-time activity probability trajectories, called functional connectivity pathways, which provide a characterization of functional brain networks.

We present a quantitative statistical analysis of pairwise crossings for all fibers obtained from whole brain tractography that confirms with high confidence that the brain grid theory (Wedeen et al., 2012a ) is not supported by the evidence. The overall fiber tracts structure appears to be more consistent with small angle treelike branching of tracts rather than with near-orthogonal gridlike crossing of fiber sheets. The analysis uses our new method for high-resolution whole brain tractography that is capable of resolving fibers crossing of less than 10 degrees and correctly following a continuous angular distribution of fibers even when the individual fiber directions are not resolved. This analysis also allows us to demonstrate that the whole brain fiber pathway system is very well approximated by a lamellar vector field, providing a concise and quantitative mathematical characterization of the structural connectivity of the human brain.

We have developed a method for the simultaneous estimation of local diffusion and the global fiber tracts based upon the information entropy flow that computes the maximum entropy trajectories between locations and depends upon the global structure of the multi-dimensional and multi-modal diffusion field. Computation of the entropy spectrum pathways requires only solving a simple eigenvector problem for the probability distribution for which efficient numerical routines exist, and a straight forward integration of the probability conservation through ray tracing of the convective modes guided by a global structure of the entropy spectrum coupled with a small scale local diffusion. The intervoxel diffusion is sampled by multi b-shell multi q-angle diffusion weighted imaging data expanded in spherical waves. This novel approach to fiber tracking incorporates global information about multiple fiber crossings in every individual voxel and ranks it in the most scientifically rigorous way. This method has potential significance for a wide range of applications, including studies of brain connectivity.

MOTIVATION: Explosive growth of short-read sequencing technologies in the recent years resulted in rapid development of many new alignment algorithms and programs. But most of them are not efficient or not applicable for reads > or approximately equal to 200 bp because these algorithms specifically designed to process short queries with relatively low sequencing error rates. However, the current trend to increase reliability of detection of structural variations in assembled genomes as well as to facilitate de novo sequencing demand complimenting high-throughput short-read platforms with long-read mapping. Thus, algorithms and programs for efficient mapping of longer reads are becoming crucial. However, the choice of long-read aligners effective in terms of both performance and memory are limited and includes only handful of hash table (BLAT, SSAHA2) or trie (Burrows-Wheeler Transform - Smith-Waterman (BWT-SW), Burrows-Wheeler Alignerr - Smith-Waterman (BWA-SW)) based algorithms. RESULTS: New O(n) algorithm that combines the advantages of both hash and trie-based methods has been designed to effectively align long biological sequences (> or approximately equal to 200 bp) against a large sequence database with small memory footprint (e.g. ~2 GB for the human genome). The algorithm is accurate and significantly more fast than BLAT or BWT-SW, but similar to BWT-SW it can find all local alignments. It is as accurate as SSAHA2 or BWA-SW, but uses 3+ times less memory and 10+ times faster than SSAHA2, several times faster than BWA-SW with low error rates and almost two times less memory. AVAILABILITY AND IMPLEMENTATION: The prototype implementation of the algorithm will be available upon request for non-commercial use in academia (local hit table binary and indices are at ftp://styx.ucsd.edu).

MOTIVATION: The analysis of high-throughput experiment data provided by microarrays becomes increasingly more and more important part of modern biological science. Microarrays allow to conduct genotyping or gene expression experiments on hundreds of thousands of test genes in parallel. Because of the large and constantly growing amount of experimental data the necessity of efficiency, robustness and complete automation of microarray image analysis algorithms is gaining significant attention in the field of microarray processing. RESULTS: The author presents here an efficient and completely automatic image registration algorithm (that is an algorithm for spots and blocks indexing) that allows to process a wide variety of microarray slides with different parameters of grid and block spacing as well as spot sizes. The algorithm scales linearly with the grid size, the time complexity is O(M), where M is number of rows x number of columns. It can successfully cope with local and global distortions of the grid, such as focal distortions and non-orthogonal transformations. The algorithm has been tested both on CCD and scanned images and showed very good performance-the processing time of a single slide with 44 blocks of 200 x 200 grid points (or 1 760 000 grid points total) was about 10 s. AVAILABILITY: The test implementation of the algorithm will be available upon request for academics. SUPPLEMENTARY INFORMATION: http://fleece.ucsd.edu/~vit/Registration_Supplement.pdf

MOTIVATION: In the first part of this paper the author presented an efficient, robust and completely automated algorithm for spot and block indexing in microarray images with rectangular grids. Although the rectangular grid is currently the most common type of grouping the probes on microarray slides, there is another microarray technology based on bundles of optical fibers where the probes are packed in hexagonal grids. The hexagonal grid provides both advantages and drawbacks over the standard rectangular packing and of course requires adaptation and/or modification of the algorithm of spot indexing presented in the first part of the paper. RESULTS: In the second part of the paper the author presents a version of the spot indexing algorithm adapted for microarray images with spots packed in hexagonal structures. The algorithm is completely automated, works with hexagonal grids of different types and with different parameters of grid spacing and rotation as well as spot sizes. It can successfully trace the local and global distortions of the grid, including non-orthogonal transformations. Similar to the algorithm from part I, it scales linearly with the grid size, the time complexity is O(M), where M is total number of grid points in hexagonal grid. The algorithm has been tested both on CCD and scanned images with spot expression rates as low as 2%. The processing time of an image with about 50 000 hex grid points was less than a second. For images with high expression rates ( approximately 90%) the registration time is even smaller, around a quarter of a second. SUPPLEMENTARY INFORMATION: http://fleece.ucsd.edu/~vit/Registration_Supplement.pdf