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Statistical considerations underpinning an alignment-free sequence comparison method
Junmei Jing,Conrad J. Burden,Sylvain Forêt,Susan R. Wilson 한국통계학회 2010 Journal of the Korean Statistical Society Vol.39 No.3
The D2 statistic is defined as the number of word matches of prespecified length k, with up to t mismatches, shared between two given sequences. This statistic finds its application in alignment-free comparisons of biological sequences. It has two main advantages over alignment-based methods for nucleotide and amino-acid sequence comparisons, such as BLAST (basic local alignment search tool). These are (i)D2 does not assume that homologous segments are contiguous, and (ii) the algorithm is computationally extremely fast, the runtime being proportional to the size of the sequences in the case of exact matches. This review article summarises results to date on determining the distributional properties of the D2 statistic for a range of biologically relevant parameters, describes existing applications of the method, and outlines future research directions.
Huh, Y.H.,Noh, M.,Burden, F.R.,Chen, J.C.,Winkler, D.A.,Sherley, J.L. Elsevier 2015 Stem cell research Vol.14 No.2
There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify such useful and specific DSC biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel ''pattern-specific biomarker'' for asymmetrically self-renewing cells, with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.
David Price,Henry Chrystyn,Alan Kaplan,John Haughney,Miguel Román-Rodríguez,Annie Burden,Alison Chisholm,Elizabeth V. Hillyer,Julie von Ziegenweidt,Muzammil Ali,Thys van der Molen 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.4
Purpose: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy. Methods: This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma,oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma). Results: Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15;95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452). Conclusions: These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.