Framework for morphometric classification of cells in imaging flow cytometry

Imaging flow cytometry is an emerging technology that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy. It allows high-throughput imaging of cells with good spatial resolution, while they are in flow. This paper proposes a general framework for the processing/classification of cells imaged using imaging flow cytometer. Each cell is localized by finding an accurate cell contour. Then, features reflecting cell size, circularity and complexity are extracted for the classification using SVM. Unlike the conventional iterative, semi-automatic segmentation algorithms such as active contour, we propose a noniterative, fully automatic graph-based cell localization. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using custom fabricated cost-effective microfluidics-based imaging flow cytometer. The proposed system is a significant development in the direction of building a cost-effective cell analysis platform that would facilitate affordable mass screening camps looking cellular morphology for disease diagnosis. Lay description In this article, we propose a novel framework for processing the raw data generated using microfluidics based imaging flow cytometers. Microfluidics microscopy or microfluidics based imaging flow cytometry (mIFC) is a recent microscopy paradigm, that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy, which allows us imaging cells while they are in flow. In comparison to the conventional slide-based imaging systems, mIFC is a nascent technology enabling high throughput imaging of cells and is yet to take the form of a clinical diagnostic tool. The proposed framework process the raw data generated by the mIFC systems. The framework incorporates several steps: beginning from pre-processing of the raw video frames to enhance the contents of the cell, localising the cell by a novel, fully automatic, non-iterative graph based algorithm, extraction of different quantitative morphological parameters and subsequent classification of cells. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using cost-effective microfluidics based imaging flow cytometer. The cell lines of HL60, K562 and MOLT were obtained from ATCC (American Type Culture Collection) and are separately cultured in the lab. Thus, each culture contains cells from its own category alone and thereby provides the ground truth. Each cell is localised by finding a closed cell contour by defining a directed, weighted graph from the Canny edge images of the cell such that the closed contour lies along the shortest weighted path surrounding the centroid of the cell from a starting point on a good curve segment to an immediate endpoint. Once the cell is localised, morphological features reflecting size, shape and complexity of the cells are extracted and used to develop a support vector machine based classification system. We could classify the cell-lines with good accuracy and the results were quite consistent across different cross validation experiments. We hope that imaging flow cytometers equipped with the proposed framework for image processing would enable cost-effective, automated and reliable disease screening in over-loaded facilities, which cannot afford to hire skilled personnel in large numbers. Such platforms would potentially facilitate screening camps in low income group countries; thereby transforming the current health care paradigms by enabling rapid, automated diagnosis for diseases like cancer.

Convex analysis for minimizing and learning submodular set functions

The connections between convexity and submodularity are explored, for purposes of minimizing and learning submodular set functions.

First, we develop a novel method for minimizing a particular class of submodular functions, which can be expressed as a sum of concave functions composed with modular functions. The basic algorithm uses an accelerated first order method applied to a smoothed version of its convex extension. The smoothing algorithm is particularly novel as it allows us to treat general concave potentials without needing to construct a piecewise linear approximation as with graph-based techniques.

Second, we derive the general conditions under which it is possible to find a minimizer of a submodular function via a convex problem. This provides a framework for developing submodular minimization algorithms. The framework is then used to develop several algorithms that can be run in a distributed fashion. This is particularly useful for applications where the submodular objective function consists of a sum of many terms, each term dependent on a small part of a large data set.

Lastly, we approach the problem of learning set functions from an unorthodox perspective---sparse reconstruction. We demonstrate an explicit connection between the problem of learning set functions from random evaluations and that of sparse signals. Based on the observation that the Fourier transform for set functions satisfies exactly the conditions needed for sparse reconstruction algorithms to work, we examine some different function classes under which uniform reconstruction is possible.

On the use of qualitative reasoning to simulate and identify metabolic pathways

King, R.D., Garrett, S.M., Coghill, G.M. (2005). On the use of qualitative reasoning to simulate and identify metabolic pathways. Bioinformatics 21(9):2017-2026 RAE2008

On Learning Counting Functions With Queries

We investigate the problem of learning disjunctions of counting functions, which are general cases of parity and modulo functions, with equivalence and membership queries. We prove that, for any prime number p, the class of disjunctions of integer-weighted counting functions with modulus p over the domain Znq (or Zn) for any given integer q ≥ 2 is polynomial time learnable using at most n + 1 equivalence queries, where the hypotheses issued by the learner are disjunctions of at most n counting functions with weights from Zp. The result is obtained through learning linear systems over an arbitrary field. In general a counting function may have a composite modulus. We prove that, for any given integer q ≥ 2, over the domain Zn2, the class of read-once disjunctions of Boolean-weighted counting functions with modulus q is polynomial time learnable with only one equivalence query, and the class of disjunctions of log log n Boolean-weighted counting functions with modulus q is polynomial time learnable. Finally, we present an algorithm for learning graph-based counting functions.

On the Intrinsic Locality Properties of Web Reference Streams

There has been considerable work done in the study of Web reference streams: sequences of requests for Web objects. In particular, many studies have looked at the locality properties of such streams, because of the impact of locality on the design and performance of caching and prefetching systems. However, a general framework for understanding why reference streams exhibit given locality properties has not yet emerged. In this work we take a first step in this direction, based on viewing the Web as a set of reference streams that are transformed by Web components (clients, servers, and intermediaries). We propose a graph-based framework for describing this collection of streams and components. We identify three basic stream transformations that occur at nodes of the graph: aggregation, disaggregation and filtering, and we show how these transformations can be used to abstract the effects of different Web components on their associated reference streams. This view allows a structured approach to the analysis of why reference streams show given properties at different points in the Web. Applying this approach to the study of locality requires good metrics for locality. These metrics must meet three criteria: 1) they must accurately capture temporal locality; 2) they must be independent of trace artifacts such as trace length; and 3) they must not involve manual procedures or model-based assumptions. We describe two metrics meeting these criteria that each capture a different kind of temporal locality in reference streams. The popularity component of temporal locality is captured by entropy, while the correlation component is captured by interreference coefficient of variation. We argue that these metrics are more natural and more useful than previously proposed metrics for temporal locality. We use this framework to analyze a diverse set of Web reference traces. We find that this framework can shed light on how and why locality properties vary across different locations in the Web topology. For example, we find that filtering and aggregation have opposing effects on the popularity component of the temporal locality, which helps to explain why multilevel caching can be effective in the Web. Furthermore, we find that all transformations tend to diminish the correlation component of temporal locality, which has implications for the utility of different cache replacement policies at different points in the Web.

Generalized Laplacian Eigenmaps for Modeling and Tracking Human Motions

This paper presents generalized Laplacian eigenmaps, a novel dimensionality reduction approach designed to address stylistic variations in time series. It generates compact and coherent continuous spaces whose geometry is data-driven. This paper also introduces graph-based particle filter, a novel methodology conceived for efficient tracking in low dimensional space derived from a spectral dimensionality reduction method. Its strengths are a propagation scheme, which facilitates the prediction in time and style, and a noise model coherent with the manifold, which prevents divergence, and increases robustness. Experiments show that a combination of both techniques achieves state-of-the-art performance for human pose tracking in underconstrained scenarios.

Overcoming the Scalability Challenges of Epidemic Simulations on Blue Waters

Modeling dynamical systems represents an important application class covering a wide range of disciplines including but not limited to biology, chemistry, finance, national security, and health care. Such applications typically involve large-scale, irregular graph processing, which makes them difficult to scale due to the evolutionary nature of their workload, irregular communication and load imbalance. EpiSimdemics is such an application simulating epidemic diffusion in extremely large and realistic social contact networks. It implements a graph-based system that captures dynamics among co-evolving entities. This paper presents an implementation of EpiSimdemics in Charm++ that enables future research by social, biological and computational scientists at unprecedented data and system scales. We present new methods for application-specific processing of graph data and demonstrate the effectiveness of these methods on a Cray XE6, specifically NCSA's Blue Waters system.

Probabilistic Inference in Credal Networks: New Complexity Results

Credal networks are graph-based statistical models whose parameters take values in a set, instead of being sharply specified as in traditional statistical models (e.g., Bayesian networks). The computational complexity of inferences on such models depends on the irrelevance/independence concept adopted. In this paper, we study inferential complexity under the concepts of epistemic irrelevance and strong independence. We show that inferences under strong independence are NP-hard even in trees with binary variables except for a single ternary one. We prove that under epistemic irrelevance the polynomial-time complexity of inferences in credal trees is not likely to extend to more general models (e.g., singly connected topologies). These results clearly distinguish networks that admit efficient inferences and those where inferences are most likely hard, and settle several open questions regarding their computational complexity. We show that these results remain valid even if we disallow the use of zero probabilities. We also show that the computation of bounds on the probability of the future state in a hidden Markov model is the same whether we assume epistemic irrelevance or strong independence, and we prove an analogous result for inference in Naive Bayes structures. These inferential equivalences are important for practitioners, as hidden Markov models and Naive Bayes networks are used in real applications of imprecise probability.

On the Complexity of Strong and Epistemic Credal Networks

Credal networks are graph-based statistical models whose parameters take values on a set, instead of being sharply specified as in traditional statistical models (e.g., Bayesian networks). The result of inferences with such models depends on the irrelevance/independence concept adopted. In this paper, we study the computational complexity of inferences under the concepts of epistemic irrelevance and strong independence. We strengthen complexity results by showing that inferences with strong independence are NP-hard even in credal trees with ternary variables, which indicates that tractable algorithms, including the existing one for epistemic trees, cannot be used for strong independence. We prove that the polynomial time of inferences in credal trees under epistemic irrelevance is not likely to extend to more general models, because the problem becomes NP-hard even in simple polytrees. These results draw a definite line between networks with efficient inferences and those where inferences are hard, and close several open questions regarding the computational complexity of such models.

Moranapho : apprentissage non supervisé de la morphologie d'une langue par généralisation de relations analogiques

Récemment, nous avons pu observer un intérêt grandissant pour l'application de l'analogie formelle à l'analyse morphologique. L'intérêt premier de ce concept repose sur ses parallèles avec le processus mental impliqué dans la création de nouveaux termes basée sur les relations morphologiques préexistantes de la langue. Toutefois, l'utilisation de ce concept reste tout de même marginale due notamment à son coût de calcul élevé.Dans ce document, nous présenterons le système à base de graphe Moranapho fondé sur l'analogie formelle. Nous démontrerons par notre participation au Morpho Challenge 2009 (Kurimo:10) et nos expériences subséquentes, que la qualité des analyses obtenues par ce système rivalise avec l'état de l'art. Nous analyserons aussi l'influence de certaines de ses composantes sur la qualité des analyses morphologiques produites. Nous appuierons les conclusions tirées de nos analyses sur des théories bien établies dans le domaine de la linguistique. Ceci nous permet donc de fournir certaines prédictions sur les succès et les échecs de notre système, lorsqu'appliqué à d'autres langues que celles testées au cours de nos expériences.

Apprentissage machine efficace : théorie et pratique

Malgré des progrès constants en termes de capacité de calcul, mémoire et quantité de données disponibles, les algorithmes d'apprentissage machine doivent se montrer efficaces dans l'utilisation de ces ressources. La minimisation des coûts est évidemment un facteur important, mais une autre motivation est la recherche de mécanismes d'apprentissage capables de reproduire le comportement d'êtres intelligents. Cette thèse aborde le problème de l'efficacité à travers plusieurs articles traitant d'algorithmes d'apprentissage variés : ce problème est vu non seulement du point de vue de l'efficacité computationnelle (temps de calcul et mémoire utilisés), mais aussi de celui de l'efficacité statistique (nombre d'exemples requis pour accomplir une tâche donnée). Une première contribution apportée par cette thèse est la mise en lumière d'inefficacités statistiques dans des algorithmes existants. Nous montrons ainsi que les arbres de décision généralisent mal pour certains types de tâches (chapitre 3), de même que les algorithmes classiques d'apprentissage semi-supervisé à base de graphe (chapitre 5), chacun étant affecté par une forme particulière de la malédiction de la dimensionalité. Pour une certaine classe de réseaux de neurones, appelés réseaux sommes-produits, nous montrons qu'il peut être exponentiellement moins efficace de représenter certaines fonctions par des réseaux à une seule couche cachée, comparé à des réseaux profonds (chapitre 4). Nos analyses permettent de mieux comprendre certains problèmes intrinsèques liés à ces algorithmes, et d'orienter la recherche dans des directions qui pourraient permettre de les résoudre. Nous identifions également des inefficacités computationnelles dans les algorithmes d'apprentissage semi-supervisé à base de graphe (chapitre 5), et dans l'apprentissage de mélanges de Gaussiennes en présence de valeurs manquantes (chapitre 6). Dans les deux cas, nous proposons de nouveaux algorithmes capables de traiter des ensembles de données significativement plus grands. Les deux derniers chapitres traitent de l'efficacité computationnelle sous un angle différent. Dans le chapitre 7, nous analysons de manière théorique un algorithme existant pour l'apprentissage efficace dans les machines de Boltzmann restreintes (la divergence contrastive), afin de mieux comprendre les raisons qui expliquent le succès de cet algorithme. Finalement, dans le chapitre 8 nous présentons une application de l'apprentissage machine dans le domaine des jeux vidéo, pour laquelle le problème de l'efficacité computationnelle est relié à des considérations d'ingénierie logicielle et matérielle, souvent ignorées en recherche mais ô combien importantes en pratique.

Performance evaluation of routing protocols for MANETs with known connectivity patterns using evolving graphs

The assessment of routing protocols for mobile wireless networks is a difficult task, because of the networks` dynamic behavior and the absence of benchmarks. However, some of these networks, such as intermittent wireless sensors networks, periodic or cyclic networks, and some delay tolerant networks (DTNs), have more predictable dynamics, as the temporal variations in the network topology can be considered as deterministic, which may make them easier to study. Recently, a graph theoretic model-the evolving graphs-was proposed to help capture the dynamic behavior of such networks, in view of the construction of least cost routing and other algorithms. The algorithms and insights obtained through this model are theoretically very efficient and intriguing. However, there is no study about the use of such theoretical results into practical situations. Therefore, the objective of our work is to analyze the applicability of the evolving graph theory in the construction of efficient routing protocols in realistic scenarios. In this paper, we use the NS2 network simulator to first implement an evolving graph based routing protocol, and then to use it as a benchmark when comparing the four major ad hoc routing protocols (AODV, DSR, OLSR and DSDV). Interestingly, our experiments show that evolving graphs have the potential to be an effective and powerful tool in the development and analysis of algorithms for dynamic networks, with predictable dynamics at least. In order to make this model widely applicable, however, some practical issues still have to be addressed and incorporated into the model, like adaptive algorithms. We also discuss such issues in this paper, as a result of our experience.

Personalised Grid Service Discovery

The authors take a broad view that ultimately Grid- or Web-services must be located via personalised, semantic-rich discovery processes. They argue that such processes must rely on the storage of arbitrary metadata about services that originates from both service providers and service users. Examples of such metadata are reliability metrics, quality of service data, or semantic service description markup. This paper presents UDDI-MT, an extension to the standard UDDI service directory approach that supports the storage of such metadata via a tunnelling technique that ties the metadata store to the original UDDI directory. They also discuss the use of a rich, graph-based RDF query language for syntactic queries on this data. Finally, they analyse the performance of each of these contributions in our implementation.

Personalised Grid Service Discovery

We take a broad view that ultimately Grid- or Web-services must be located via personalised, semantic-rich discovery processes. We argue that such processes must rely on the storage of arbitrary metadata about services that originates from both service providers and service users. Examples of such metadata are reliability metrics, quality of service data, or semantic service description markup. This paper presents UDDI-MT, an extension to the standard UDDI service directory approach that supports the storage of such metadata via a tunnelling technique that ties the metadata store to the original UDDI directory. We also discuss the use of a rich, graph-based RDF query language for syntactic queries on this data. Finally, we analyse the performance of each of these contributions in our implementation.