22 research outputs found

    Efficient method for estimating the number of communities in a network

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    While there exist a wide range of effective methods for community detection in networks, most of them require one to know in advance how many communities one is looking for. Here we present a method for estimating the number of communities in a network using a combination of Bayesian inference with a novel prior and an efficient Monte Carlo sampling scheme. We test the method extensively on both real and computer-generated networks, showing that it performs accurately and consistently, even in cases where groups are widely varying in size or structure.Comment: 13 pages, 4 figure

    Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

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    Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

    Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

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    Direct Gas-Chromatographic Determination of Methanol in Alcoholic Beverages

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    A gas.chromatographic method on a semicapillary column for a rapid and quantitative determination of methanol in distillates, alcoholic beverages and wines is described. The internal standard is acetone, detection limit is 0.02% methanol with reference to ethanol

    Statistical methods for constructing disease comorbidity networks from longitudinal inpatient data

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    Tools from network science can be utilized to study relations between diseases. Different studies focus on different types of inter-disease linkages. One of them is the comorbidity patterns derived from large-scale longitudinal data of hospital discharge records. Researchers seek to describe comorbidity relations as a network to characterize pathways of disease progressions and to predict future risks. The first step in such studies is the construction of the network itself, which subsequent analyses rest upon. There are different ways to build such a network. In this paper, we provide an overview of several existing statistical approaches in network science applicable to weighted directed networks. We discuss the differences between the null models that these models assume and their applications. We apply these methods to the inpatient data of approximately one million people, spanning approximately 17 years, pertaining to the Montreal Census Metropolitan Area. We discuss the differences in the structure of the networks built by different methods, and different features of the comorbidity relations that they extract. We also present several example applications of these methods. Keywords: Weighted networks; Null model; Comorbidity; Disease networks; Centralit

    Geography, Host Genetics, and Cross‐Domain Microbial Networks Structure the Skin Microbiota of Fragmented Brazilian Atlantic Forest Frog Populations

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    The host‐associated microbiome plays a significant role in health. However, the roles of factors such as host genetics and microbial interactions in determining microbiome diversity remain unclear. We examined these factors using amplicon‐based sequencing of 175 Thoropa taophora frog skin swabs collected from a naturally fragmented landscape in southeastern Brazil. Specifically, we examined (1) the effects of geography and host genetics on microbiome diversity and structure; (2) the structure of microbial eukaryotic and bacterial co‐occurrence networks; and (3) co‐occurrence between microeukaryotes with bacterial OTUs known to affect growth of the fungal pathogen Batrachochytrium dendrobatidis (Bd). While bacterial alpha diversity varied by both site type and host MHC IIB genotype, microeukaryotic alpha diversity varied only by site type. However, bacteria and microeukaryote composition showed variation according to both site type and host MHC IIB genotype. Our network analysis showed the highest connectivity when both eukaryotes and bacteria were included, implying that ecological interactions may occur among domains. Lastly, anti‐Bd bacteria were not broadly negatively co‐associated with the fungal microbiome and were positively associated with potential amphibian parasites. Our findings emphasize the importance of considering both domains in microbiome research and suggest that for effective probiotic strategies for amphibian disease management, considering potential interactions among all members of the microbiome is crucial.We use a natural laboratory to examine the relationship between host genetic diversity, bacterial diversity, and microeukaryote diversity in the skin microbiome of a Brazilian frog. We find that host immunogenetic diversity is associated with variation in microbiome diversity and structure, and present results that support novel associations between microeukaryotes and bacteria on frog skin. Our results have implications for the relationships between host genetics and health mediated through microbiome diversity and structure.​Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168518/1/ece37594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168518/2/ece37594_am.pd
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