3,777 research outputs found
Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas.
Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naĂŻve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations
Guest Editorial Special Issue on Medical Imaging and Image Computing in Computational Physiology
International audienceThe January 2013 Special Issue of IEEE transactions on medical imaging discusses papers on medical imaging and image computing in computational physiology. Aslanid and co-researchers present an experimental technique based on stained micro computed tomography (CT) images to construct very detailed atrial models of the canine heart. The paper by Sebastian proposes a model of the cardiac conduction system (CCS) based on structural information derived from stained calf tissue. Ho, Mithraratne and Hunter present a numerical simulation of detailed cerebral venous flow. The third category of papers deals with computational methods for simulating medical imagery and incorporate knowledge of imaging physics and physiology/biophysics. The work by Morales showed how the combination of device modeling and virtual deployment, in addition to patient-specific image-based anatomical modeling, can help to carry out patient-specific treatment plans and assess alternative therapeutic strategies
Multimodal Network Alignment
A multimodal network encodes relationships between the same set of nodes in
multiple settings, and network alignment is a powerful tool for transferring
information and insight between a pair of networks. We propose a method for
multimodal network alignment that computes a matrix which indicates the
alignment, but produces the result as a low-rank factorization directly. We
then propose new methods to compute approximate maximum weight matchings of
low-rank matrices to produce an alignment. We evaluate our approach by applying
it on synthetic networks and use it to de-anonymize a multimodal transportation
network.Comment: 14 pages, 6 figures, Siam Data Mining 201
Dwelling Quietly in the Rich Club: Brain Network Determinants of Slow Cortical Fluctuations
For more than a century, cerebral cartography has been driven by
investigations of structural and morphological properties of the brain across
spatial scales and the temporal/functional phenomena that emerge from these
underlying features. The next era of brain mapping will be driven by studies
that consider both of these components of brain organization simultaneously --
elucidating their interactions and dependencies. Using this guiding principle,
we explored the origin of slowly fluctuating patterns of synchronization within
the topological core of brain regions known as the rich club, implicated in the
regulation of mood and introspection. We find that a constellation of densely
interconnected regions that constitute the rich club (including the anterior
insula, amygdala, and precuneus) play a central role in promoting a stable,
dynamical core of spontaneous activity in the primate cortex. The slow time
scales are well matched to the regulation of internal visceral states,
corresponding to the somatic correlates of mood and anxiety. In contrast, the
topology of the surrounding "feeder" cortical regions show unstable, rapidly
fluctuating dynamics likely crucial for fast perceptual processes. We discuss
these findings in relation to psychiatric disorders and the future of
connectomics.Comment: 35 pages, 6 figure
Supervised cross-modal factor analysis for multiple modal data classification
In this paper we study the problem of learning from multiple modal data for
purpose of document classification. In this problem, each document is composed
two different modals of data, i.e., an image and a text. Cross-modal factor
analysis (CFA) has been proposed to project the two different modals of data to
a shared data space, so that the classification of a image or a text can be
performed directly in this space. A disadvantage of CFA is that it has ignored
the supervision information. In this paper, we improve CFA by incorporating the
supervision information to represent and classify both image and text modals of
documents. We project both image and text data to a shared data space by factor
analysis, and then train a class label predictor in the shared space to use the
class label information. The factor analysis parameter and the predictor
parameter are learned jointly by solving one single objective function. With
this objective function, we minimize the distance between the projections of
image and text of the same document, and the classification error of the
projection measured by hinge loss function. The objective function is optimized
by an alternate optimization strategy in an iterative algorithm. Experiments in
two different multiple modal document data sets show the advantage of the
proposed algorithm over other CFA methods
Stochastic modelling and analysis of metabolic heterogeneity in single cells
A wide range of cellular processes are inherently stochastic. While stochasticity of gene transcription and translation or cellular growth profiles is well-understood, little is known about the stochastic properties of metabolism. Recent experimental findings strongly suggest that metabolism may indeed be subject to stochastic phenomena, which has questioned the traditional deterministic view of metabolism and casts crucial doubt on the general validity of this modelling paradigm. In this thesis, we examine stochastic aspects of metabolic reactions in detail. We focus on stochastic versions of classic deterministic models for metabolic reactions coupled with well-established stochastic models for gene expression. We incorporate experimental measurements of kinetic parameters in the study, which results in a specific multiscale structure of the presented class of models. In the course of this thesis, we present numerous models with increasing complexity, focussing on three key contributions. Firstly, we present the derivation of an analytical tool to approximate stationary metabolite distributions in closed-form by exploiting the multiple scales. As a result, we propose a strikingly-accurate analytical tool for exploring the parameter space. Secondly, we reveal which parameters have strong impacts on the stationary metabolite distributions and identify conditions for increased coefficients of variation and highly-complex bimodal and multimodal patterns. Finally, we propose a general strategy to obtain closed-form approximations in more complex models, such as multi-step pathways and regulatory processes commonly found in metabolism, such as allostery or end-product inhibition. The results in this thesis lay the groundwork for future studies of metabolic heterogeneity and offer numerous biological hypotheses that could soon be tested in light of recent progress in single-cell measurements of cellular metabolites.Open Acces
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