Revisiting the Training of Logic Models of Protein Signaling Networks with a Formal Approach based on Answer Set Programming

A fundamental question in systems biology is the construction and training to data of mathematical models. Logic formalisms have become very popular to model signaling networks because their simplicity allows us to model large systems encompassing hundreds of proteins. An approach to train (Boolean) logic models to high-throughput phospho-proteomics data was recently introduced and solved using optimization heuristics based on stochastic methods. Here we demonstrate how this problem can be solved using Answer Set Programming (ASP), a declarative problem solving paradigm, in which a problem is encoded as a logical program such that its answer sets represent solutions to the problem. ASP has significant improvements over heuristic methods in terms of efficiency and scalability, it guarantees global optimality of solutions as well as provides a complete set of solutions. We illustrate the application of ASP with in silico cases based on realistic networks and data

Trusted Computing and Secure Virtualization in Cloud Computing

Large-scale deployment and use of cloud computing in industry is accompanied and in the same time hampered by concerns regarding protection of data handled by cloud computing providers. One of the consequences of moving data processing and storage off company premises is that organizations have less control over their infrastructure. As a result, cloud service (CS) clients must trust that the CS provider is able to protect their data and infrastructure from both external and internal attacks. Currently however, such trust can only rely on organizational processes declared by the CS provider and can not be remotely verified and validated by an external party. Enabling the CS client to verify the integrity of the host where the virtual machine instance will run, as well as to ensure that the virtual machine image has not been tampered with, are some steps towards building trust in the CS provider. Having the tools to perform such verifications prior to the launch of the VM instance allows the CS clients to decide in runtime whether certain data should be stored- or calculations should be made on the VM instance offered by the CS provider. This thesis combines three components -- trusted computing, virtualization technology and cloud computing platforms -- to address issues of trust and security in public cloud computing environments. Of the three components, virtualization technology has had the longest evolution and is a cornerstone for the realization of cloud computing. Trusted computing is a recent industry initiative that aims to implement the root of trust in a hardware component, the trusted platform module. The initiative has been formalized in a set of specifications and is currently at version 1.2. Cloud computing platforms pool virtualized computing, storage and network resources in order to serve a large number of customers customers that use a multi-tenant multiplexing model to offer on-demand self-service over broad network. Open source cloud computing platforms are, similar to trusted computing, a fairly recent technology in active development. The issue of trust in public cloud environments is addressed by examining the state of the art within cloud computing security and subsequently addressing the issues of establishing trust in the launch of a generic virtual machine in a public cloud environment. As a result, the thesis proposes a trusted launch protocol that allows CS clients to verify and ensure the integrity of the VM instance at launch time, as well as the integrity of the host where the VM instance is launched. The protocol relies on the use of Trusted Platform Module (TPM) for key generation and data protection. The TPM also plays an essential part in the integrity attestation of the VM instance host. Along with a theoretical, platform-agnostic protocol, the thesis also describes a detailed implementation design of the protocol using the OpenStack cloud computing platform. In order the verify the implementability of the proposed protocol, a prototype implementation has built using a distributed deployment of OpenStack. While the protocol covers only the trusted launch procedure using generic virtual machine images, it presents a step aimed to contribute towards the creation of a secure and trusted public cloud computing environment

Eigenvector Centrality Distribution for Characterization of Protein Allosteric Pathways

Determining the principal energy pathways for allosteric communication in biomolecules, that occur as a result of thermal motion, remains challenging due to the intrinsic complexity of the systems involved. Graph theory provides an approach for making sense of such complexity, where allosteric proteins can be represented as networks of amino acids. In this work, we establish the eigenvector centrality metric in terms of the mutual information, as a mean of elucidating the allosteric mechanism that regulates the enzymatic activity of proteins. Moreover, we propose a strategy to characterize the range of the physical interactions that underlie the allosteric process. In particular, the well known enzyme, imidazol glycerol phosphate synthase (IGPS), is utilized to test the proposed methodology. The eigenvector centrality measurement successfully describes the allosteric pathways of IGPS, and allows to pinpoint key amino acids in terms of their relevance in the momentum transfer process. The resulting insight can be utilized for refining the control of IGPS activity, widening the scope for its engineering. Furthermore, we propose a new centrality metric quantifying the relevance of the surroundings of each residue. In addition, the proposed technique is validated against experimental solution NMR measurements yielding fully consistent results. Overall, the methodologies proposed in the present work constitute a powerful and cost effective strategy to gain insight on the allosteric mechanism of proteins

Signed Network Modeling Based on Structural Balance Theory

The modeling of networks, specifically generative models, have been shown to provide a plethora of information about the underlying network structures, as well as many other benefits behind their construction. Recently there has been a considerable increase in interest for the better understanding and modeling of networks, but the vast majority of this work has been for unsigned networks. However, many networks can have positive and negative links(or signed networks), especially in online social media, and they inherently have properties not found in unsigned networks due to the added complexity. Specifically, the positive to negative link ratio and the distribution of signed triangles in the networks are properties that are unique to signed networks and would need to be explicitly modeled. This is because their underlying dynamics are not random, but controlled by social theories, such as Structural Balance Theory, which loosely states that users in social networks will prefer triadic relations that involve less tension. Therefore, we propose a model based on Structural Balance Theory and the unsigned Transitive Chung-Lu model for the modeling of signed networks. Our model introduces two parameters that are able to help maintain the positive link ratio and proportion of balanced triangles. Empirical experiments on three real-world signed networks demonstrate the importance of designing models specific to signed networks based on social theories to obtain better performance in maintaining signed network properties while generating synthetic networks.Comment: CIKM 2018: https://dl.acm.org/citation.cfm?id=327174