Maurizio Drocco

Stochastic Calculus of Wrapped Compartments

The Calculus of Wrapped Compartments (CWC) is a variant of the Calculus of Looping Sequences(CLS). While keeping the same expressiveness, CWC strongly simplifies the development of auto-matic tools for the analysis of biological systems. The main simplification consists in the removal ofthe sequencing operator, thus lightening the formal treatment of the patterns to be matched in a term(whose complexity in CLS is strongly affected by the variables matching in the sequences).We define a stochastic semantics for this new calculus. As an application we model the interac-tion between macrophages and apoptotic neutrophils and a mechanism of gene regulation in E.Coli.

On Designing Multicore-Aware Simulators for Biological Systems

The stochastic simulation of biological systems is an increasingly popular technique in bioinformatics. It often is an enlightening technique, which may however result in being computational expensive. We discuss the main opportunities to speed it up on multi-core platforms, which pose new challenges for parallelisation techniques. These opportunities are developed in two general families of solutions involving both the single simulation and a bulk of independent simulations (either replicas of derived from parameter sweep). Proposed solutions are tested on the parallelisation of the CWC simulator (Calculus of Wrapped Compartments) that is carried out according to proposed solutions by way of the Fast Flow programming framework making possible fast development and efficient execution on multi-cores.

Parallel stochastic systems biology in the cloud

The stochastic modelling of biological systems, coupled with Monte Carlo simulation of models, is an increasingly popular technique in bioinformatics. The simulation-analysis workflow may result computationally expensive reducing the interactivity required in the model tuning. In this work, we advocate the high-level software design as a vehicle for building efficient and portable parallel simulators for the cloud. In particular, the Calculus of Wrapped Components (CWC) simulator for systems biology, which is designed according to the FastFlow pattern-based approach, is presented and discussed. Thanks to the FastFlow framework, the CWC simulator is designed as a high-level workflow that can simulate CWC models, merge simulation results and statistically analyse them in a single parallel workflow in the cloud. To improve interactivity, successive phases are pipelined in such a way that the workflow begins to output a stream of analysis results immediately after simulation is started. Performance and effectiveness of the CWC simulator are validated on the Amazon Elastic Compute Cloud.

Simulation techniques for the calculus of wrapped compartments

The modelling and analysis of biological systems has deep roots in Mathematics, specifically in the field of Ordinary Differential Equations (ODEs). Alternative approaches based on formal calculi, often derived from process algebras or term rewriting systems, provide a quite complementary way to analyse the behaviour of biological systems. These calculi allow to cope in a natural way with notions like compartments and membranes, which are not easy (sometimes impossible) to handle with purely numerical approaches, and are often based on stochastic simulation methods. Recently, it has also become evident that stochastic effects in regulatory networks play a crucial role in the analysis of such systems. Actually, in many situations it is necessary to use stochastic models. For example when the system to be described is based on the interaction of few molecules, when we are at the presence of a chemical instability, or when we want to simulate the functioning of a pool of entities whose compartmentalised structure evolves dynamically. In contrast, stable metabolic networks, involving a large number of reagents, for which the computational cost of a stochastic simulation becomes an insurmountable obstacle, are efficiently modelled with ODEs. In this paper we define a hybrid simulation method, combining the stochastic approach with ODEs, for systems described in the Calculus of Wrapped Compartments (CWC), a calculus on which we can express the compartmentalisation of a biological system whose evolution is defined by a set of rewrite rules.

Modelling ammonium transporters in arbuscular mycorrhiza symbiosis

The Stochastic Calculus ofWrapped Compartments (SCWC) is a recently proposed variant of the Stochastic Calculus of Looping Sequences (SCLS), a language for the representation and simulation of biological systems. In this work we apply SCWC to model a newly discovered ammonium transporter. This transporter is believed to play a fundamental role for plant mineral acquisition, which takes place in the arbuscular mycorrhiza, the most wide-spread plant-fungus symbiosis on earth. Investigating this kind of symbiosis is considered one of the most promising ways to develop methods to nurture plants in more natural manners, avoiding the complex chemical productions used nowadays to produce artificial fertilizers. In our experiments the passage of NH3 / NH+4 from the fungus to the plant has been dissected in known and hypothetical mechanisms; with the model so far we have been able to simulate the behavior of the system under different conditions. Our simulations confirmed some of the latest experimental results about the LjAMT2;2 transporter. Moreover, by comparing the behaviour of LjAMT2;2 with the behaviour of another ammonium transporter which exists in plants, viz. LjAMT1;1, our simulations support an hypothesis about why LjAMT2;2 is so selectively expressed in arbusculated cells.

Parallel visual data restoration on multi-GPGPUs using stencil-reduce pattern

In this paper, a highly effective parallel filter for visual data restoration is presented. The filter is designed following a skeletal approach, using a newly proposed stencil-reduce, and has been implemented by way of the FastFlow parallel programming library. As a result of its high-level design, it is possible to run the filter seamlessly on a multicore machine, on multi-GPGPUs, or on both. The design and implementation of the filter are discussed, and an experimental evaluation is presented.

A parallel edge preserving algorithm for salt and pepper image denoising

In this paper a two-phase filter for removing “salt and pepper” noise is proposed. In the first phase, an adaptive median filter is used to identify the set of the noisy pixels; in the second phase, these pixels are restored according to a regularization method, which contains a data-fidelity term reflecting the impulse noise characteristics. The algorithm, which exhibits good performance both in denoising and in restoration, can be easily and effectively parallelized to exploit the full power of multi-core CPUs and GPGPUs; the proposed implementation based on the FastFlow library achieves both close-to-ideal speedup and very good wall-clock execution figures.

On parallelizing on-line statistics for stochastic biological simulations

This work concerns a general technique to enrich parallel version of stochastic simulators for biological systems with tools for on-line statistical analysis of the results. In particular, within the FastFlow parallel programming framework, we describe the methodology and the implementation of a parallel Monte Carlo simulation infrastructure extended with user-defined on-line data filtering and mining functions. The simulator and the on-line analysis were validated on large multi-core platforms and representative proof-of-concept biological systems.

A Comparison of Big Data Frameworks on a Layered Dataflow Model

In the world of Big Data analytics, there is a series of tools aiming at simplifying programming applications to be executed on clusters. Although each tool claims to provide better programming, data and execution models, for which only informal (and often confusing) semantics is generally provided, all share a common underlying model, namely, the Dataflow model. The Dataflow model we propose shows how various tools share the same expressiveness at different levels of abstraction. The contribution of this work is twofold: first, we show that the proposed model is (at least) as general as existing batch and streaming frameworks (e.g., Spark, Flink, Storm), thus making it easier to understand high-level data-processing applications written in such frameworks. Second, we provide a layered model that can represent tools and applications following the Dataflow paradigm and we show how the analyzed tools fit in each level.

Integrating Multi-omic features exploiting Chromosome Conformation Capture data

The representation, integration, and interpretation of omic data is a complex task, in particular considering the huge amount of information that is daily produced in molecular biology laboratories all around the world. The reason is that sequencing data regarding expression profiles, methylation patterns, and chromatin domains is difficult to harmonize in a systems biology view, since genome browsers only allow coordinate-based representations, discarding functional clusters created by the spatial conformation of the DNA in the nucleus. In this context, recent progresses in high throughput molecular biology techniques and bioinformatics have provided insights into chromatin interactions on a larger scale and offer a formidable support for the interpretation of multi-omic data. In particular, a novel sequencing technique called Chromosome Conformation Capture allows the analysis of the chromosome organization in the cell’s natural state. While performed genome wide, this technique is usually called Hi–C. Inspired by service applications such as Google Maps, we developed NuChart, an R package that integrates Hi–C data to describe the chromosomal neighborhood starting from the information about gene positions, with the possibility of mapping on the achieved graphs genomic features such as methylation patterns and histone modifications, along with expression profiles. In this paper we show the importance of the NuChart application for the integration of multi-omic data in a systems biology fashion, with particular interest in cytogenetic applications of these techniques. Moreover, we demonstrate how the integration of multi-omic data can provide useful information in understanding why genes are in certain specific positions inside the nucleus and how epigenetic patterns correlate with their expression.