Discovering Beaten Paths in Collaborative Ontology-Engineering Projects using Markov Chains

Biomedical taxonomies, thesauri and ontologies in the form of the International Classification of Diseases (ICD) as a taxonomy or the National Cancer Institute Thesaurus as an OWL-based ontology, play a critical role in acquiring, representing and processing information about human health. With increasing adoption and relevance, biomedical ontologies have also significantly increased in size. For example, the 11th revision of the ICD, which is currently under active development by the WHO contains nearly 50,000 classes representing a vast variety of different diseases and causes of death. This evolution in terms of size was accompanied by an evolution in the way ontologies are engineered. Because no single individual has the expertise to develop such large-scale ontologies, ontology-engineering projects have evolved from small-scale efforts involving just a few domain experts to large-scale projects that require effective collaboration between dozens or even hundreds of experts, practitioners and other stakeholders. Understanding how these stakeholders collaborate will enable us to improve editing environments that support such collaborations. We uncover how large ontology-engineering projects, such as the ICD in its 11th revision, unfold by analyzing usage logs of five different biomedical ontology-engineering projects of varying sizes and scopes using Markov chains. We discover intriguing interaction patterns (e.g., which properties users subsequently change) that suggest that large collaborative ontology-engineering projects are governed by a few general principles that determine and drive development. From our analysis, we identify commonalities and differences between different projects that have implications for project managers, ontology editors, developers and contributors working on collaborative ontology-engineering projects and tools in the biomedical domain.Comment: Published in the Journal of Biomedical Informatic

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to the mouse lumbar intervertebral disc

A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries

Activity archetypes in question-and-answer (Q8A) websites—A study of 50 Stack Exchange instances

Millions of users on the Internet discuss a variety of topics on Question-and-Answer (Q&A) instances. However, not all instances and topics receive the same amount of attention, as some thrive and achieve self-sustaining levels of activity, while others fail to attract users and either never grow beyond being a small niche community or become inactive. Hence, it is imperative to not only better understand but also to distill deciding factors and rules that define and govern sustainable Q&A instances. We aim to empower community managers with quantitative methods for them to better understand, control and foster their communities, and thus contribute to making the Web a more efficient place to exchange information. To that end, we extract, model and cluster user activity-based time series from $50$ randomly selected Q&A instances from the Stack Exchange network to characterize user behavior. We find four distinct types of user activity temporal patterns, which vary primarily according to the users' activity frequency. Finally, by breaking down total activity in our 50 Q&A instances by the previously identified user activity profiles, we classify those 50 Q&A instances into three different activity profiles. Our parsimonious categorization of Q&A instances aligns with the stage of development and maturity of the underlying communities, and can potentially help operators of such instances: We not only quantitatively assess progress of Q&A instances, but we also derive practical implications for optimizing Q&A community building efforts, as we e.g. recommend which user types to focus on at different developmental stages of a Q&A community

HopRank: How semantic structure influences teleportation in PageRank (a case study on BioPortal)

This paper introduces HopRank, an algorithm for modeling human navigation on semantic networks. HopRank leverages the assumption that users know or can see the whole structure of the network. Therefore, besides following links, they also follow nodes at certain distances (i.e., k-hop neighborhoods), and not at random as suggested by PageRank, which assumes only links are known or visible. We observe such preference towards k-hop neighborhoods on BioPortal, one of the leading repositories of biomedical ontologies on the Web. In general, users navigate within the vicinity of a concept. But they also "jump" to distant concepts less frequently. We fit our model on 11 ontologies using the transition matrix of clickstreams, and show that semantic structure can influence teleportation in PageRank. This suggests that users--to some extent--utilize knowledge about the underlying structure of ontologies, and leverage it to reach certain pieces of information. Our results help the development and improvement of user interfaces for ontology exploration.Comment: Published at TheWebConf 2019 (WWW'19

How users explore ontologies on the Web: A study of NCBO's BioPortal usage logs

Ontologies in the biomedical domain are numerous, highly specialized and very expensive to develop. Thus, a crucial prerequisite for ontology adoption and reuse is effective support for exploring and finding existing ontologies. Towards that goal, the National Center for Biomedical Ontology (NCBO) has developed BioPortal---an online repository designed to support users in exploring and finding more than 500 existing biomedical ontologies. In 2016, BioPortal represents one of the largest portals for exploration of semantic biomedical vocabularies and terminologies, which is used by many researchers and practitioners. While usage of this portal is high, we know very little about how exactly users search and explore ontologies and what kind of usage patterns or user groups exist in the first place. Deeper insights into user behavior on such portals can provide valuable information to devise strategies for a better support of users in exploring and finding existing ontologies, and thereby enable better ontology reuse. To that end, we study and group users according to their browsing behavior on BioPortal using data mining techniques. Additionally, we use the obtained groups to characterize and compare exploration strategies across ontologies. In particular, we were able to identify seven distinct browsing-behavior types, which all make use of different functionality provided by BioPortal. For example, Search Explorers make extensive use of the search functionality while Ontology Tree Explorers mainly rely on the class hierarchy to explore ontologies. Further, we show that specific characteristics of ontologies influence the way users explore and interact with the website. Our results may guide the development of more user-oriented systems for ontology exploration on the Web.Comment: Under review for WWW'1

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531

Cross-Modal Transfer of Statistical Information Benefits from Sleep

Extracting regularities from a sequence of events is essential for understanding our environment. However, there is no consensus regarding the extent to which such regularities can be generalised beyond the modality of learning. One reason for this could be the variation in consolidation intervals used in different paradigms, also including an opportunity to sleep. Using a novel statistical learning paradigm in which structured information is acquired in the auditory domain and tested in the visual domain over either 30min or 24hr consolidation intervals, we show that cross-modal transfer can occur, but this transfer is only seen in the 24hr group. Importantly, the extent of cross-modal transfer is predicted by the amount of SWS obtained. Additionally, cross-modal transfer is associated with the same pattern of decreasing MTL and increasing striatal involvement which has previously been observed to occur across 24 hours in unimodal statistical learning. We also observed enhanced functional connectivity after 24 hours in a network of areas which have been implicated in cross-modal integration including the precuneus and the middle occipital gyrus. Finally, functional connectivity between the striatum and the precuneus was also enhanced, and this strengthening was predicted by SWS. These results demonstrate that statistical learning can generalise to some extent beyond the modality of acquisition, and together with our previously published unimodal results, support the notion that statistical learning is both domain-general and domain-specific

Antibody Responses to Antigenic Targets of Recent Exposure Are Associated With Low-Density Parasitemia in Controlled Human Plasmodium falciparum Infections.

The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman's ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe