Biomedical subjects

Riccardo Boscolo

Publications and source records attributed to Riccardo Boscolo.

5 recordsLinked to original sources

PubMed2004

Independent component analysis based on nonparametric density estimation.

In this paper, we introduce a novel independent component analysis (ICA) algorithm, which is truly blind to the particular underlying distribution of the mixed signals. Using a nonparametric kernel density estimation technique, the algorithm performs simultaneously the estimation of the unknown probability density functions of the source signals and the estimation of the unmixing matrix. Following the proposed approach, the blind signal separation framework can be posed as a nonlinear optimization problem, where a closed form expression of the cost function is available, and only the elements of the unmixing matrix appear as unknowns. We conducted a series of Monte Carlo simulations, involving linear mixtures of various source signals with different statistical characteristics and sample sizes. The new algorithm not only consistently outperformed all state-of-the-art ICA methods, but also demonstrated the following properties: 1) Only a flexible model, capable of learning the source statistics, can consistently achieve an accurate separation of all the mixed signals. 2) Adopting a suitably designed optimization framework, it is possible to derive a flexible ICA algorithm that matches the stability and convergence properties of conventional algorithms. 3) A nonparametric approach does not necessarily require large sample sizes in order to outperform methods with fixed or partially adaptive contrast functions.

Algorithms↗

PubMed2003

Transcriptome-based determination of multiple transcription regulator activities in Escherichia coli by using network component analysis.

Cells adjust gene expression profiles in response to environmental and physiological changes through a series of signal transduction pathways. Upon activation or deactivation, the terminal regulators bind to or dissociate from DNA, respectively, and modulate transcriptional activities on particular promoters. Traditionally, individual reporter genes have been used to detect the activity of the transcription factors. This approach works well for simple, non-overlapping transcription pathways. For complex transcriptional networks, more sophisticated tools are required to deconvolute the contribution of each regulator. Here, we demonstrate the utility of network component analysis in determining multiple transcription factor activities based on transcriptome profiles and available connectivity information regarding network connectivity. We used Escherichia coli carbon source transition from glucose to acetate as a model system. Key results from this analysis were either consistent with physiology or verified by using independent measurements.

Cyclic AMP↗

PubMed2003

Network component analysis: reconstruction of regulatory signals in biological systems.

High-dimensional data sets generated by high-throughput technologies, such as DNA microarray, are often the outputs of complex networked systems driven by hidden regulatory signals. Traditional statistical methods for computing low-dimensional or hidden representations of these data sets, such as principal component analysis and independent component analysis, ignore the underlying network structures and provide decompositions based purely on a priori statistical constraints on the computed component signals. The resulting decomposition thus provides a phenomenological model for the observed data and does not necessarily contain physically or biologically meaningful signals. Here, we develop a method, called network component analysis, for uncovering hidden regulatory signals from outputs of networked systems, when only a partial knowledge of the underlying network topology is available. The a priori network structure information is first tested for compliance with a set of identifiability criteria. For networks that satisfy the criteria, the signals from the regulatory nodes and their strengths of influence on each output node can be faithfully reconstructed. This method is first validated experimentally by using the absorbance spectra of a network of various hemoglobin species. The method is then applied to microarray data generated from yeast Saccharamyces cerevisiae and the activities of various transcription factors during cell cycle are reconstructed by using recently discovered connectivity information for the underlying transcriptional regulatory networks.

Biology↗

PubMedDate not supplied

A generalized framework for network component analysis.

The authors recently introduced a framework, named Network Component Analysis (NCA), for the reconstruction of the dynamics of transcriptional regulators' activities from gene expression assays. The original formulation had certain shortcomings that limited NCA's application to a wide class of network dynamics reconstruction problems, either because of limitations in the sample size or because of the stringent requirements imposed by the set of identifiability conditions. In addition, the performance characteristics of the method for various levels of data noise or in the presence of model inaccuracies were never investigated. In this article, the following aspects of NCA have been addressed, resulting in a set of extensions to the original framework: 1) The sufficient conditions on the a priori connectivity information (required for successful reconstructions via NCA) are made less stringent, allowing easier verification of whether a network topology is identifiable, as well as extending the class of identifiable systems. Such a result is accomplished by introducing a set of identifiability requirements that can be directly tested on the regulatory architecture, rather than on specific instances of the system matrix. 2) The two-stage least square iterative procedure used in NCA is proven to identify stationary points of the likelihood function, under Gaussian noise assumption, thus reinforcing the statistical foundations of the method. 3) A framework for the simultaneous reconstruction of multiple regulatory subnetworks is introduced, thus overcoming one of the critical limitations of the original formulation of the decomposition, for example, occurring for poorly sampled data (typical of microarray experiments). A set of monte carlo simulations we conducted with synthetic data suggests that the approach is indeed capable of accurately reconstructing regulatory signals when these are the input of large-scale networks that satisfy the suggested identifiability criteria, even under fairly noisy conditions. The sensitivity of the reconstructed signals to inaccuracies in the hypothesized network topology is also investigated. We demonstrate the feasibility of our approach for the simultaneous reconstruction of multiple regulatory subnetworks from the same data set with a successful application of the technique to gene expression measurements of the bacterium Escherichia coli.

Algorithms↗

PubMedDate not supplied

Medical image segmentation with knowledge-guided robust active contours.

Medical image segmentation techniques typically require some form of expert human supervision to provide accurate and consistent identification of anatomic structures of interest. A novel segmentation technique was developed that combines a knowledge-based segmentation system with a sophisticated active contour model. This approach exploits the guidance of a higher-level process to robustly perform the segmentation of various anatomic structures. The user need not provide initial contour placement, and the high-level process carries out the required parameter optimization automatically. Knowledge about the anatomic structures to be segmented is defined statistically in terms of probability density functions of parameters such as location, size, and image intensity (eg, computed tomographic [CT] attenuation value). Preliminary results suggest that the performance of the algorithm at chest and abdominal CT is comparable to that of more traditional segmentation techniques like region growing and morphologic operators. In some cases, the active contour-based technique may outperform standard segmentation methods due to its capacity to fully enforce the available a priori knowledge concerning the anatomic structure of interest. The active contour algorithm is particularly suitable for integration with high-level image understanding frameworks, providing a robust and easily controlled low-level segmentation tool. Further study is required to determine whether the proposed algorithm is indeed capable of providing consistently superior segmentation.

Algorithms↗