Conflicting Biomedical Assumptions for Mathematical Modeling: The Case of Cancer Metastasis

Computational models in biomedicine rely on biological and clinical assumptions. The selection of these assumptions contributes substantially to modeling success or failure. Assumptions used by experts at the cutting edge of research, however, are rarely explicitly described in scientific publications. One can directly collect and assess some of these assumptions through interviews and surveys. Here we investigate diversity in expert views about a complex biological phenomenon, the process of cancer metastasis. We harvested individual viewpoints from 28 experts in clinical and molecular aspects of cancer metastasis and summarized them computationally. While experts predominantly agreed on the definition of individual steps involved in metastasis, no two expert scenarios for metastasis were identical. We computed the probability that any two experts would disagree on k or fewer metastatic stages and found that any two randomly selected experts are likely to disagree about several assumptions. Considering the probability that two or more of these experts review an article or a proposal about metastatic cascades, the probability that they will disagree with elements of a proposed model approaches 1. This diversity of conceptions has clear consequences for advance and deadlock in the field. We suggest that strong, incompatible views are common in biomedicine but largely invisible to biomedical experts themselves. We built a formal Markov model of metastasis to encapsulate expert convergence and divergence regarding the entire sequence of metastatic stages. This model revealed stages of greatest disagreement, including the points at which cancer enters and leaves the bloodstream. The model provides a formal probabilistic hypothesis against which researchers can evaluate data on the process of metastasis. This would enable subsequent improvement of the model through Bayesian probabilistic update. Practically, we propose that model assumptions and hunches be harvested systematically and made available for modelers and scientists.</p

Conceptual knowledge acquisition in biomedicine: A methodological review

AbstractThe use of conceptual knowledge collections or structures within the biomedical domain is pervasive, spanning a variety of applications including controlled terminologies, semantic networks, ontologies, and database schemas. A number of theoretical constructs and practical methods or techniques support the development and evaluation of conceptual knowledge collections. This review will provide an overview of the current state of knowledge concerning conceptual knowledge acquisition, drawing from multiple contributing academic disciplines such as biomedicine, computer science, cognitive science, education, linguistics, semiotics, and psychology. In addition, multiple taxonomic approaches to the description and selection of conceptual knowledge acquisition and evaluation techniques will be proposed in order to partially address the apparent fragmentation of the current literature concerning this domain

PhenoGO: an integrated resource for the multiscale mining of clinical and biological data

The evolving complexity of genome-scale experiments has increasingly centralized the role of a highly computable, accurate, and comprehensive resource spanning multiple biological scales and viewpoints. To provide a resource to meet this need, we have significantly extended the PhenoGO database with gene-disease specific annotations and included an additional ten species. This a computationally-derived resource is primarily intended to provide phenotypic context (cell type, tissue, organ, and disease) for mining existing associations between gene products and GO terms specified in the Gene Ontology Databases Automated natural language processing (BioMedLEE) and computational ontology (PhenOS) methods were used to derive these relationships from the literature, expanding the database with information from ten additional species to include over 600,000 phenotypic contexts spanning eleven species from five GO annotation databases. A comprehensive evaluation evaluating the mappings (n = 300) found precision (positive predictive value) at 85%, and recall (sensitivity) at 76%. Phenotypes are encoded in general purpose ontologies such as Cell Ontology, the Unified Medical Language System, and in specialized ontologies such as the Mouse Anatomy and the Mammalian Phenotype Ontology. A web portal has also been developed, allowing for advanced filtering and querying of the database as well as download of the entire dataset

Development and validation of a pragmatic natural language processing approach to identifying falls in older adults in the emergency department

BACKGROUND: Falls among older adults are both a common reason for presentation to the emergency department, and a major source of morbidity and mortality. It is critical to identify fall patients quickly and reliably during, and immediately after, emergency department encounters in order to deliver appropriate care and referrals. Unfortunately, falls are difficult to identify without manual chart review, a time intensive process infeasible for many applications including surveillance and quality reporting. Here we describe a pragmatic NLP approach to automating fall identification. METHODS: In this single center retrospective review, 500 emergency department provider notes from older adult patients (age 65 and older) were randomly selected for analysis. A simple, rules-based NLP algorithm for fall identification was developed and evaluated on a development set of 1084 notes, then compared with identification by consensus of trained abstractors blinded to NLP results. RESULTS: The NLP pipeline demonstrated a recall (sensitivity) of 95.8%, specificity of 97.4%, precision of 92.0%, and F1 score of 0.939 for identifying fall events within emergency physician visit notes, as compared to gold standard manual abstraction by human coders. CONCLUSIONS: Our pragmatic NLP algorithm was able to identify falls in ED notes with excellent precision and recall, comparable to that of more labor-intensive manual abstraction. This finding offers promise not just for improving research methods, but as a potential for identifying patients for targeted interventions, quality measure development and epidemiologic surveillance

Conflicting biomedical assumptions for mathematical modeling: the case of cancer metastasis.

Computational models in biomedicine rely on biological and clinical assumptions. The selection of these assumptions contributes substantially to modeling success or failure. Assumptions used by experts at the cutting edge of research, however, are rarely explicitly described in scientific publications. One can directly collect and assess some of these assumptions through interviews and surveys. Here we investigate diversity in expert views about a complex biological phenomenon, the process of cancer metastasis. We harvested individual viewpoints from 28 experts in clinical and molecular aspects of cancer metastasis and summarized them computationally. While experts predominantly agreed on the definition of individual steps involved in metastasis, no two expert scenarios for metastasis were identical. We computed the probability that any two experts would disagree on k or fewer metastatic stages and found that any two randomly selected experts are likely to disagree about several assumptions. Considering the probability that two or more of these experts review an article or a proposal about metastatic cascades, the probability that they will disagree with elements of a proposed model approaches 1. This diversity of conceptions has clear consequences for advance and deadlock in the field. We suggest that strong, incompatible views are common in biomedicine but largely invisible to biomedical experts themselves. We built a formal Markov model of metastasis to encapsulate expert convergence and divergence regarding the entire sequence of metastatic stages. This model revealed stages of greatest disagreement, including the points at which cancer enters and leaves the bloodstream. The model provides a formal probabilistic hypothesis against which researchers can evaluate data on the process of metastasis. This would enable subsequent improvement of the model through Bayesian probabilistic update. Practically, we propose that model assumptions and hunches be harvested systematically and made available for modelers and scientists