The P3 platform: an approach and software system for developing diagrammatic model-based methods in design research

Many issues in design and design management have been explored by building models which capture the relationships between different aspects of the problem at hand. These models require computer support to construct and analyse. However, appropriate modelling tools can be time-consuming to develop in a research environment. Reflecting upon five design research projects, this paper proposes that such projects can be facilitated by recognising the iterative and tightly-coupled nature of research and tool development, and by attempting to minimise the effort of solution prototyping within this process. Our approach is enabled by a software platform which can be rapidly configured to implement many conceivable modelling approaches. This configurability is complemented by an emerging library of modelling and analysis approaches tailored to explore design process systems. The platform-based approach enables any mix of modelling concepts to be easily created. We propose it could thus help researchers to explore a wide range of questions without being constrained to existing conventions for modelling – or for model integration

SWIM: A computational tool to unveiling crucial nodes in complex biological networks

SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure

The Infectious Disease Ontology in the Age of COVID-19

The Infectious Disease Ontology (IDO) is a suite of interoperable ontology modules that aims to provide coverage of all aspects of the infectious disease domain, including biomedical research, clinical care, and public health. IDO Core is designed to be a disease and pathogen neutral ontology, covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is then extended by a collection of ontology modules focusing on specific diseases and pathogens. In this paper we present applications of IDO Core within various areas of infectious disease research, together with an overview of all IDO extension ontologies and the methodology on the basis of which they are built. We also survey recent developments involving IDO, including the creation of IDO Virus; the Coronaviruses Infectious Disease Ontology (CIDO); and an extension of CIDO focused on COVID-19 (IDO-CovID-19).We also discuss how these ontologies might assist in information-driven efforts to deal with the ongoing COVID-19 pandemic, to accelerate data discovery in the early stages of future pandemics, and to promote reproducibility of infectious disease research

A Model of Function-Based Representations

The need to model and to reason about design alternatives throughout the design process demands robust representation schemes of function, behavior, and structure. Function describes the physical effect imposed on an energy or material flow by a design entity without regard for the working principles or physical solutions used to accomplish this effect. Behaviors are the physical events associated with a physical artifact (or hypothesized concept) over time (or simulated time) as perceived by an observer. Structure, the most tangible concept, partitions an artifact into meaningful constituents such as features, Wirk elements, and interfaces in addition to the widely used assemblies and components. The focus of this work is on defining a model for function-based representations that can be used across various design methodologies and for a variety of design tasks throughout all stages of the design process. In particular, the mapping between function and structure is explored and, to a lesser extent, its impact on behavior is noted. Clearly, the issues of a function-based representation\u27s composition and mappings directly impact certain computational synthesis methods that rely on (digitally) archived product design knowledge. Moreover, functions have already been related to not only form, but also information of user actions, performance parameters in the form of equations, and failure mode data. It is essential to understand the composition and mappings of functions and their relation to design activities because this information is part of the foundation for function-based methods, and consequently dictates the performance of those methods. Toward this end, the important findings of this work include a formalism for two aspects of function-based representations (composition and mappings), the supported design activities of the model for function-based representations, and examples of how computational design methods benefit from this formalism

Convergent evolution of modularity in metabolic networks through different community structures

Background: It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of themodularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. Results: In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxomony. Conclusions: We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organismﾒs metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network communities that better correspond to functional categorizations

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Explain3D: Explaining Disagreements in Disjoint Datasets

Data plays an important role in applications, analytic processes, and many aspects of human activity. As data grows in size and complexity, we are met with an imperative need for tools that promote understanding and explanations over data-related operations. Data management research on explanations has focused on the assumption that data resides in a single dataset, under one common schema. But the reality of today's data is that it is frequently un-integrated, coming from different sources with different schemas. When different datasets provide different answers to semantically similar questions, understanding the reasons for the discrepancies is challenging and cannot be handled by the existing single-dataset solutions. In this paper, we propose Explain3D, a framework for explaining the disagreements across disjoint datasets (3D). Explain3D focuses on identifying the reasons for the differences in the results of two semantically similar queries operating on two datasets with potentially different schemas. Our framework leverages the queries to perform a semantic mapping across the relevant parts of their provenance; discrepancies in this mapping point to causes of the queries' differences. Exploiting the queries gives Explain3D an edge over traditional schema matching and record linkage techniques, which are query-agnostic. Our work makes the following contributions: (1) We formalize the problem of deriving optimal explanations for the differences of the results of semantically similar queries over disjoint datasets. (2) We design a 3-stage framework for solving the optimal explanation problem. (3) We develop a smart-partitioning optimizer that improves the efficiency of the framework by orders of magnitude. (4)~We experiment with real-world and synthetic data to demonstrate that Explain3D can derive precise explanations efficiently