The core-periphery model for protein interaction (PPI) networks assumes that protein complexes in these networks consist of a dense core and a possibly sparse periphery that is adjacent to vertices ...in the core of the complex. In this work, we aim at uncovering a global core-periphery structure for a given PPI network. We propose two exact graph-theoretic formulations for this task, which aim to fit the input network to a hypothetical ground truth network by a minimum number of edge modifications. In one model each cluster has its own periphery, and in the other the periphery is shared. We first analyze both models from a theoretical point of view, showing their NP-hardness. Then, we devise efficient exact and heuristic algorithms for both models and finally perform an evaluation on subnetworks of the S. cerevisiae PPI network.
In the network querying problem, one is given a protein complex or pathway of species A and a protein-protein interaction network of species B; the goal is to identify subnetworks of B that are ...similar to the query in terms of sequence, topology, or both. Existing approaches mostly depend on knowledge of the interaction topology of the query in the network of species A; however, in practice, this topology is often not known. To address this problem, we develop a topology-free querying algorithm, which we call Torque. Given a query, represented as a set of proteins, Torque seeks a matching set of proteins that are sequence-similar to the query proteins and span a connected region of the network, while allowing both insertions and deletions. The algorithm uses alternatively dynamic programming and integer linear programming for the search task. We test Torque with queries from yeast, fly, and human, where we compare it to the QNet topology-based approach, and with queries from less studied species, where only topology-free algorithms apply. Torque detects many more matches than QNet, while giving results that are highly functionally coherent.
TORQUE is a tool for cross-species querying of protein-protein interaction networks. It aims to answer the following question: given a set of proteins constituting a known complex or a pathway in one ...species, can a similar complex or pathway be found in the protein network of another species? To this end, TORQUE seeks a matching set of proteins that are sequence similar to the query proteins and span a connected region of the target network, while allowing for both insertions and deletions. Unlike existing approaches, TORQUE does not require knowledge of the interconnections among the query proteins. It can handle large queries of up to 25 proteins. The TORQUE web server is freely available for use at http://www.cs.tau.ac.il/~bnet/torque.html.
The NP-hard Colorful Components problem is, given a vertex-colored graph, to delete a minimum number of edges such that no connected component contains two vertices of the same color. It has ...applications in multiple sequence alignment and in multiple network alignment where the colors correspond to species. We initiate a systematic complexity-theoretic study of Colorful Components by presenting NP-hardness as well as fixed-parameter tractability results for different variants of Colorful Components. We also perform experiments with our algorithms and additionally develop an efficient and very accurate heuristic algorithm clearly outperforming a previous min-cut-based heuristic on multiple sequence alignment data.
In the network querying problem, one is given a protein complex or pathway of species A and a protein–protein interaction network of species B; the goal is to identify subnetworks of B that are ...similar to the query. Existing approaches mostly depend on knowledge of the interaction topology of the query in the network of species A; however, in practice, this topology is often not known. To combat this problem, we develop a topology-free querying algorithm, which we call Torque. Given a query, represented as a set of proteins, Torque seeks a matching set of proteins that are sequence-similar to the query proteins and span a connected region of the network, while allowing both insertions and deletions. The algorithm uses alternatively dynamic programming and integer linear programming for the search task. We test Torque with queries from yeast, fly, and human, where we compare it to the QNet topology-based approach, and with queries from less studied species, where only topology-free algorithms apply. Torque detects many more matches than QNet, while in both cases giving results that are highly functionally coherent.
IMPORTANCE: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including ...age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. OBJECTIVES: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. EXPOSURES: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). MAIN OUTCOMES AND MEASURES: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. RESULTS: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 81.0%), followed by RDEB (218 of 283 77.0%), DDEB (71 of 104 68.3%), and EBS (100 of 194 51.5%). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. CONCLUSIONS AND RELEVANCE: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.
Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling.
To describe diagnostic testing patterns and assess diagnostic ...concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB.
A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal.
A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%).
Retrospective design.
Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.
Background/Objectives
Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, ...and bacterial‐host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad‐scale analysis of wound cultures.
Methods
A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018.
Results
Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty‐eight percent of patients had cultures positive for methicillin‐sensitive SA, and 47%, methicillin‐resistant SA (18 patients had cultures that grew both methicillin‐susceptible and methicillin‐resistant SA at different points in time). Of 15 patients with SA‐positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin‐susceptible SA and 6 patients mupirocin‐resistant SA (2 patients grew both mupirocin‐susceptible and mupirocin‐resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively.
Conclusions
SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.
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