Functional brain segmentation using inter-subject correlation in fMRI.

The human brain continuously processes massive amounts of rich sensory information. To better understand such highly complex brain processes, modern neuroimaging studies are increasingly utilizing experimental setups that better mimic daily-life situations. A new exploratory data-analysis approach, functional segmentation inter-subject correlation analysis (FuSeISC), was proposed to facilitate the analysis of functional magnetic resonance (fMRI) data sets collected in these experiments. The method provides a new type of functional segmentation of brain areas, not only characterizing areas that display similar processing across subjects but also areas in which processing across subjects is highly variable. FuSeISC was tested using fMRI data sets collected during traditional block-design stimuli (37 subjects) as well as naturalistic auditory narratives (19 subjects). The method identified spatially local and/or bilaterally symmetric clusters in several cortical areas, many of which are known to be processing the types of stimuli used in the experiments. The method is not only useful for spatial exploration of large fMRI data sets obtained using naturalistic stimuli, but also has other potential applications, such as generation of a functional brain atlases including both lower- and higher-order processing areas. Finally, as a part of FuSeISC, a criterion-based sparsification of the shared nearest-neighbor graph was proposed for detecting clusters in noisy data. In the tests with synthetic data, this technique was superior to well-known clustering methods, such as Ward's method, affinity propagation, and K-means ++. Hum Brain Mapp 38:2643-2665, 2017. © 2017 Wiley Periodicals, Inc.

Error-corrected estimation of regional kinetic parameter histograms directly from pet projections.

Positron emission tomography (PET) is a unique method to investigate physiology in the living body. Kinetic models with kinetic rate constants describe the dynamic radioactive tracer uptake in living tissue. If the variation of the kinetic parameter values within a specific tissue region could be determined accurately, it would give valuable quantitative information about the tissue heterogeneity. In this study we developed a unique method to estimate the variation from the regional kinetic parameter histograms. To determine the kinetic parameter values, we chose non-penalized maximum likelihood (ML) estimation due to the specific statistical error properties of the ML estimates. The parameter values were estimated directly from the time series of PET projections. The choice of the estimation method enabled us to utilize the ML theory in error correction. We developed a Monte Carlo approach to determine the regional error distributions. The true variation of the kinetic parameters could then be revealed by correcting the regional ML estimate histograms with the estimated error distributions. The method was tested with simulated data. In simulations both the average and the deviation of the kinetic parameters were determined from the error-corrected histograms with good numerical accuracy for the selected region of interest.

RMBNToolbox: random models for biochemical networks.

BACKGROUND: There is an increasing interest to model biochemical and cell biological networks, as well as to the computational analysis of these models. The development of analysis methodologies and related software is rapid in the field. However, the number of available models is still relatively small and the model sizes remain limited. The lack of kinetic information is usually the limiting factor for the construction of detailed simulation models. RESULTS: We present a computational toolbox for generating random biochemical network models which mimic real biochemical networks. The toolbox is called Random Models for Biochemical Networks. The toolbox works in the Matlab environment, and it makes it possible to generate various network structures, stoichiometries, kinetic laws for reactions, and parameters therein. The generation can be based on statistical rules and distributions, and more detailed information of real biochemical networks can be used in situations where it is known. The toolbox can be easily extended. The resulting network models can be exported in the format of Systems Biology Markup Language. CONCLUSION: While more information is accumulating on biochemical networks, random networks can be used as an intermediate step towards their better understanding. Random networks make it possible to study the effects of various network characteristics to the overall behavior of the network. Moreover, the construction of artificial network models provides the ground truth data needed in the validation of various computational methods in the fields of parameter estimation and data analysis.

Stochastic dynamic model for estimation of rate constants and their variances from noisy and heterogeneous PET measurements.

Tissue heterogeneity, radioactive decay and measurement noise are the main error sources in compartmental modeling used to estimate the physiologic rate constants of various radiopharmaceuticals from a dynamic PET study. We introduce a new approach to this problem by modeling the tissue heterogeneity with random rate constants in compartment models. In addition, the Poisson nature of the radioactive decay is included as a Poisson random variable in the measurement equations. The estimation problem will be carried out using the maximum likelihood estimation. With this approach, we do not only get accurate mean estimates for the rate constants, but also estimates for tissue heterogeneity within the region of interest and other possibly unknown model parameters, e.g. instrument noise variance, as well. We also avoid the problem of the optimal weighting of the data related to the conventionally used weighted least-squares method. The new approach was tested with simulated time-activity curves from the conventional three compartment - three rate constants model with normally distributed rate constants and with a noise mixture of Poisson and normally distributed random variables. Our simulation results showed that this new model gave accurate estimates for the mean of the rate constants, the measurement noise parameter and also for the tissue heterogeneity, i.e. for the variance of the rate constants within the region of interest.

Global gene expression profile of human cord blood-derived CD133+ cells.

Human cord blood (CB)-derived CD133+ cells carry characteristics of primitive hematopoietic cells and proffer an alternative for CD34+ cells in hematopoietic stem cell (HSC) transplantation. To characterize the CD133+ cell population on a genetic level, a global expression analysis of CD133+ cells was performed using oligonucleotide microarrays. CD133+ cells were purified from four fresh CB units by immunomagnetic selection. All four CD133+ samples showed significant similarity in their gene expression pattern, whereas they differed clearly from the CD133- control samples. In all, 690 transcripts were differentially expressed between CD133+ and CD133- cells. Of these, 393 were increased and 297 were decreased in CD133+ cells. The highest overexpression was noted in genes associated with metabolism, cellular physiological processes, cell communication, and development. A set of 257 transcripts expressed solely in the CD133+ cell population was identified. Colony-forming unit (CFU) assay was used to detect the clonal progeny of precursors present in the studied cell populations. The results demonstrate that CD133+ cells express primitive markers and possess clonogenic progenitor capacity. This study provides a gene expression profile for human CD133+ cells. It presents a set of genes that may be used to unravel the properties of the CD133+ cell population, assumed to be highly enriched in HSCs.

Transcriptional profiling reflects shared and unique characters for CD34+ and CD133+ cells.

CD34 and CD133 are the most commonly used markers to enrich hematopoietic stem cells (HSCs). Positively selected HSCs are increasingly used for autologous and allogeneic transplantation, yet the biological properties of CD34(+) and CD133(+) cells are largely unknown. In the present study, a genome-wide gene expression analysis of human cord blood (CB)-derived CD34(+) cells was performed. The CD34(+) gene expression profile was compared to an identically constructed CD133(+) gene expression profile to reveal the specific expression patterns and major differences of CD34(+) and CD133(+) cells. As expected, many genes were similarly expressed in the two cell populations, but cell-type-specific gene expression was also demonstrated. Self-organizing map analysis was used to identify transcripts having similar expression patterns, and the results were compared between CD34(+) and CD133(+) cells. Also, a prioritization algorithm was used to rank the genes best separating CD34(+) and CD133(+) cells from their CD34() and CD133() counterparts in CB. Our results show that CD133(+) cells have higher numbers of up-regulated genes than CD34(+) cells. Furthermore, the uniquely expressed genes in CD34(+) or CD133(+) cell populations were associated with different biological processes. CD34(+) cells overexpressed many transcripts associated with development and response to stress or external stimuli. In CD133(+) cells, the most significantly represented biological processes were establishment and maintenance of chromatin architecture, DNA metabolism, and cell cycle. The differences between the gene expression profiles of CD34(+) and CD133(+) cells indicate the more primitive nature of CD133(+) cells. These profiles suggest that CD34(+) and CD133(+) cells may have different roles in hematopoietic regeneration.