Bringing LTL Model Checking to Biologists

The BioModelAnalyzer (BMA) is a web based tool for the development of discrete models of biological systems. Through a graphical user interface, it allows rapid development of complex models of gene and protein interaction networks and stability analysis without requiring users to be proficient computer programmers. Whilst stability is a useful specification for testing many systems, testing temporal specifications in BMA presently requires the user to perform simulations. Here we describe the LTL module, which includes a graphical and natural language interfaces to testing LTL queries. The graphical interface allows for graphical construction of the queries and presents results visually in keeping with the current style of BMA. The Natural language interface complements the graphical interface by allowing a gentler introduction to formal logic and exposing educational resources

Finding Instability in Biological Models

Abstract. The stability of biological models is an important test for es-tablishing their soundness and accuracy. Stability in biological systems represents the ability of a robust system to always return to homeosta-sis. In recent work, modular approaches for proving stability have been found to be swift and scalable. If stability is however not proved, the currently available techniques apply an exhaustive search through the unstable state space to find loops. This search is frequently prohibitively computationally expensive, limiting its usefulness. Here we present a new modular approach eliminating the need for an exhaustive search for loops. Using models of biological systems we show that the technique finds loops significantly faster than brute force approaches. Furthermore, for a subset of stable systems which are resistant to modular proofs, we observe a speed up of up to 3 orders of magnitude as the exhaustive searches for loops which cause instability are avoided. With our new procedure we are able to prove instability and stability in a number of realistic biological models, including adaptation in bacterial chemotaxis, the lambda phage lysogeny/lysis switch, voltage gated channel opening and cAMP oscillations in the slime mold Dictyostelium discoideum. This new approach will support the development of new clinically relevant tools for industrial biomedicine

Model-Checking Signal Transduction Networks through Decreasing Reachability Sets

Abstract. We consider model checking of Qualitative Networks, a popular formalism for modeling signal transduction networks in biology. One of the unique features of qualitative networks, due to them lacking initial states, is that of “reducing reachability sets”. Simply put, a state that is not visited after i steps will not be visited after i ′ steps for every i ′> i. We use this feature to create a compact representation of all the paths of a qualitative network of a certain structure. Combining this compact path representation with LTL model checking leads to significant acceleration in performance. In particular, for a recent model of Leukemia, our approach works at least 5 times faster than the standard approach and up to 100 times faster in some cases. Our approach enhances the iterative hypothesis-driven experimentation process used by biologists, enabling fast turn-around of executable biological models.

A comparative study on the use of a HA/collagen/chondroitin sulphate biomaterial (Biostite) and a bovine-derived HA xenograft (Bio-Oss) in the treatment of deep intra-osseous defects

OBJECTIVES: This parallel-group, randomized, clinical trial was designed to evaluate the clinical outcome of deep intra-osseous defects following reconstructive surgery with the use of a synthetic hydroxyapatite/equine Type I collagen/chondroitin sulphate biomaterial (Biostite), as compared to a bovine-derived hydroxyapatite xenograft (Bio-Oss). MATERIAL AND METHODS: Twenty-four systemically healthy subjects with moderate to advanced periodontitis, 11 females and 13 males, aged 30-64 years, seven smokers, were selected. Patients presented with one interproximal deep intra-osseous defect (intra-osseous component >or=4 mm) as clinically and radiographically evaluated. Immediately before surgery and 12 months after surgery, pocket probing depth (PPD), clinical attachment level (CAL) and radiographic depth of the defect (DEPTH) were evaluated. RESULTS: Thirteen defects were treated with Biostite (test) and 11 defects with Bio-Oss (control). In the test group, PPD amounted to 7.8+/-1.3 mm before surgery, and decreased significantly to 3.6+/-1.6 mm 12 months following surgery, while in the control group PPD significantly decreased from 7.5+/-2.0 mm pre-surgery to 3.1+/-1.0 mm post-surgery. At 1 year, CAL gain and DEPTH gain were 2.9+/-1.9 and 2.5+/-1.4 mm, respectively, in the test group, and 4.0+/-2.4 mm and 3.1+/-1.8 mm, respectively, in the control group. No statistically significant differences for PPD reduction, CAL gain and DEPTH gain were detected between the groups. CONCLUSIONS: The results of the present study indicate that both Biostite and Bio-Oss grafting biomaterials have determined a clinically and statistically significant improvement in terms of CAL gain, PPD reduction and radiographic DEPTH gain when used for the treatment of deep intra-osseous defects