Choice Of Modeling Framework Research Articles

Exploring the Niche of Rickettsia montanensis (Rickettsiales: Rickettsiaceae) Infection of the American Dog Tick (Acari: Ixodidae), Using Multiple Species Distribution Model Approaches.

The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), is a vector for several human disease-causing pathogens such as tularemia, Rocky Mountain spotted fever, and the understudied spotted fever group rickettsiae (SFGR) infection caused by Rickettsia montanensis. It is important for public health planning and intervention to understand the distribution of this tick and pathogen encounter risk. Risk is often described in terms of vector distribution, but greatest risk may be concentrated where more vectors are positive for a given pathogen. When assessing species distributions, the choice of modeling framework and spatial layers used to make predictions are important. We first updated the modeled distribution of D. variabilis and R. montanensis using maximum entropy (MaxEnt), refining bioclimatic data inputs, and including soil variables. We then compared geospatial predictions from five species distribution modeling frameworks. In contrast to previous work, we additionally assessed whether the R. montanensis positive D. variabilis distribution is nested within a larger overall D. variabilis distribution, representing a fitness cost hypothesis. We found that 1) adding soil layers improved the accuracy of the MaxEnt model; 2) the predicted ‘infected niche’ was smaller than the overall predicted niche across all models; and 3) each model predicted different sizes of suitable niche, at different levels of probability. Importantly, the models were not directly comparable in output style, which could create confusion in interpretation when developing planning tools. The random forest (RF) model had the best measured validity and fit, suggesting it may be most appropriate to these data.

Hypergraph-based connectivity measures for signaling pathway topologies.

Characterizing cellular responses to different extrinsic signals is an active area of research, and curated pathway databases describe these complex signaling reactions. Here, we revisit a fundamental question in signaling pathway analysis: are two molecules "connected" in a network? This question is the first step towards understanding the potential influence of molecules in a pathway, and the answer depends on the choice of modeling framework. We examined the connectivity of Reactome signaling pathways using four different pathway representations. We find that Reactome is very well connected as a graph, moderately well connected as a compound graph or bipartite graph, and poorly connected as a hypergraph (which captures many-to-many relationships in reaction networks). We present a novel relaxation of hypergraph connectivity that iteratively increases connectivity from a node while preserving the hypergraph topology. This measure, B-relaxation distance, provides a parameterized transition between hypergraph connectivity and graph connectivity. B-relaxation distance is sensitive to the presence of small molecules that participate in many functionally unrelated reactions in the network. We also define a score that quantifies one pathway's downstream influence on another, which can be calculated as B-relaxation distance gradually relaxes the connectivity constraint in hypergraphs. Computing this score across all pairs of 34 Reactome pathways reveals pairs of pathways with statistically significant influence. We present two such case studies, and we describe the specific reactions that contribute to the large influence score. Finally, we investigate the ability for connectivity measures to capture functional relationships among proteins, and use the evidence channels in the STRING database as a benchmark dataset. STRING interactions whose proteins are B-connected in Reactome have statistically significantly higher scores than interactions connected in the bipartite graph representation. Our method lays the groundwork for other generalizations of graph-theoretic concepts to hypergraphs in order to facilitate signaling pathway analysis.

Connectivity measures for signaling pathway topologies

Abstract Characterizing cellular responses to different extrinsic signals is an active area of research, and curated pathway databases describe these complex signaling reactions. Here, we revisit a fundamental question in signaling pathway analysis: are two molecules “connected” in a network? This question is the first step towards understanding the potential influence of molecules in a pathway, and the answer depends on the choice of modeling framework. We examined the connectivity of Reactome signaling pathways using four different pathway representations. We find that Reactome is very well connected as a graph, moderately well connected as a compound graph or bipartite graph, and poorly connected as a hypergraph (which captures many-to-many relationships in reaction networks). We present a novel relaxation of hypergraph connectivity that iteratively increases connectivity from a node while preserving the hypergraph topology. This measure, B-relaxation distance, provides a parameterized transition between hypergraph connectivity and graph connectivity. B-relaxation distance is sensitive to the presence of small molecules that participate in many functionally unrelated reactions in the network. We also define a score that quantifies one pathway’s downstream influence on another, which can be calculated as B-relaxation distance gradually relaxes the connectivity constraint in hypergraphs. Computing this score across all pairs of 34 Reactome pathways reveals pairs of pathways statistically significant influence. We present two such case studies, and we describe the specific reactions that contribute to the large influence score. Finally, we investigate the ability for connectivity measures to capture functional relationships among proteins, and use the evidence channels in the STRING database as a benchmark dataset. STRING interactions whose proteins are B-connected in Reactome have statistically significantly higher scores than interactions connected in the bipartite graph representation. Our method lays the groundwork for other generalizations of graph-theoretic concepts to hypergraphs in order to facilitate signaling pathway analysis. Author summary Signaling pathways describe how cells respond to external signals through molecular interactions. As we gain a deeper understanding of these signaling reactions, it is important to understand how molecules may influence downstream responses and how pathways may affect each other. As the amount of information in signaling pathway databases continues to grow, we have the opportunity to analyze properties about pathway structure. We pose an intuitive question about signaling pathways: when are two molecules “connected” in a pathway? This answer varies dramatically based on the assumptions we make about how reactions link molecules. Here, examine four approaches for modeling the structural topology of signaling pathways, and present methods to quantify whether two molecules are “connected” in a pathway database. We find that existing approaches are either too permissive (molecules are connected to many others) or restrictive (molecules are connected to a handful of others), and we present a new measure that offers a continuum between these two extremes. We then expand our question to ask when an entire signaling pathway is “downstream” of another pathway, and show two case studies from the Reactome pathway database that uncovers pathway influence. Finally, we show that the strict notion of connectivity can capture functional relationships among proteins using an independent benchmark dataset. Our approach to quantify connectivity in pathways considers a biologically-motivated definition of connectivity, laying the foundation for more sophisticated analyses that leverage the detailed information in pathway databases.

Issues in extractive resource taxation: A review of research methods and models

This paper provides a conceptual overview of economists′ attempts to learn about the effects of taxes on extractive resources. The emphasis is on research methods and techniques, with no attempt to provide a comprehensive tabulation of previous empirical results or policy conclusions regarding preferred tax instruments or systems. We argue, in fact, that the nature of such conclusions largely depends on, and is limited by, the researcher′s choice of modeling framework. Many alternative frameworks and approaches have been developed in the literature. Our goal is to describe the differences among them and to note their strengths and limitations.

Issues in Extractive Resource Taxation: A Review of Research Methods and Models

This paper provides a conceptual overview of economists’ attempts to learn about the effects of taxes on extractive resources. The emphasis is on research methods and techniques, with no attempt to provide a comprehensive tabulation of previous empirical results or policy conclusions regarding preferred tax instruments or systems. We argue, in fact, that the nature of such conclusions largely depends on the researcher’s choice of modeling framework. Many alternative frameworks and approaches have been developed in the literature. Our goal is to describe the differences among them and to note their strengths and limitations.

Issues in Extractive Resource Taxation: A Review of Research Methods and Models

This paper provides a conceptual overview of economists' attempts to learn about the effects of taxes on extractive resources. The emphasis is on research methods and techniques, with no attempt to provide a comprehensive tabulation of previous empirical results or policy conclusions regarding preferred tax instruments or systems. We argue, in fact, that the nature of such conclusions largely depends on the researcher's choice of modeling framework. Many alternative frameworks and approaches have been developed in the literature. Our goal is to describe the differences among them and to note their strengths and limitations.