Fixed confidence community mode estimation

Our aim is to estimate the largest community (a.k.a., mode) in a population composed of multiple disjoint communities. This estimation is performed in a fixed confidence setting via sequential sampling of individuals with replacement. We consider two sampling models: (i) an identityless model, wherein only the community of each sampled individual is revealed, and (ii) an identity-based model, wherein the learner is able to discern whether or not each sampled individual has been sampled before, in addition to the community of that individual. The former model corresponds to the classical problem of identifying the mode of a discrete distribution, whereas the latter seeks to capture the utility of identity information in mode estimation. For each of these models, we establish information theoretic lower bounds on the expected number of samples needed to meet the prescribed confidence level, and propose sound algorithms with a sample complexity that is provably asymptotically optimal. Our analysis highlights that identity information can indeed be utilized to improve the efficiency of community mode estimation.Comment: To appear in Performance Evaluatio

Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease

Rates of pediatric Crohn’s disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. Nontargeted metabolite profiling of urine samples from CD (n = 18) and UC (n = 8) in a pediatric retrospective cohort study was performed using multisegment injection-capillary electrophoresis-mass spectrometry. Over 122 urinary metabolites were reliably measured from pediatric IBD patients, and unknown metabolites were identified by tandem mass spectrometry. Dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CS) in repeat urine samples collected over 8 weeks. Higher urinary excretion of indoxyl sulfate, hydroxyindoxyl sulfate, phenylacetylglutamine, and sialic acid were measured in CD as compared to UC patients, but lower threonine, serine, kynurenine, and hypoxanthine (p < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (AUC = 0.972; p = 3.21 × 10−5). Urinary octanoyl glucuronide, pantothenic acid, and pyridoxic acid were also identified as specific dietary biomarkers of EEN in pediatric IBD patients who achieved clinical remission. This work may complement or replace existing strategies in the diagnosis and early management of children with IBD

The centaurin γ-1 GTPase-like domain functions as an NTPase

Centaurins are a family of proteins that contain GTPase-activating protein domains, with the γ family members containing in addition a GTPase-like domain. Centaurins reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. In the present study, using X-ray structural analysis, enzymatic assays and nucleotide-binding studies, we show that, for CENTG1 (centaurin γ-1) the GTPase-like domain has broader trinucleotide specificity. Alterations within the G4 motif of CENTG1 from the highly conserved NKXD found in typical GTPases to TQDR result in the loss of specificity, a lower affinity for the nucleotides and higher turnover rates. These results indicate that the centaurins could be more accurately classified as NTPases and point to alternative mechanisms of cell signalling control