8,587 research outputs found
Diffusive hidden Markov model characterization of DNA looping dynamics in tethered particle experiments
In many biochemical processes, proteins bound to DNA at distant sites are
brought into close proximity by loops in the underlying DNA. For example, the
function of some gene-regulatory proteins depends on such DNA looping
interactions. We present a new technique for characterizing the kinetics of
loop formation in vitro, as observed using the tethered particle method, and
apply it to experimental data on looping induced by lambda repressor. Our
method uses a modified (diffusive) hidden Markov analysis that directly
incorporates the Brownian motion of the observed tethered bead. We compare
looping lifetimes found with our method (which we find are consistent over a
range of sampling frequencies) to those obtained via the traditional
threshold-crossing analysis (which can vary depending on how the raw data are
filtered in the time domain). Our method does not involve any time filtering
and can detect sudden changes in looping behavior. For example, we show how our
method can identify transitions between long-lived, kinetically distinct states
that would otherwise be difficult to discern
Deep learning extends de novo protein modelling coverage of genomes using iteratively predicted structural constraints
The inapplicability of amino acid covariation methods to small protein
families has limited their use for structural annotation of whole genomes.
Recently, deep learning has shown promise in allowing accurate residue-residue
contact prediction even for shallow sequence alignments. Here we introduce
DMPfold, which uses deep learning to predict inter-atomic distance bounds, the
main chain hydrogen bond network, and torsion angles, which it uses to build
models in an iterative fashion. DMPfold produces more accurate models than two
popular methods for a test set of CASP12 domains, and works just as well for
transmembrane proteins. Applied to all Pfam domains without known structures,
confident models for 25% of these so-called dark families were produced in
under a week on a small 200 core cluster. DMPfold provides models for 16% of
human proteome UniProt entries without structures, generates accurate models
with fewer than 100 sequences in some cases, and is freely available.Comment: JGG and SMK contributed equally to the wor
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Noninvasive prenatal diagnosis of 21-Hydroxylase deficiency using target capture sequencing of maternal plasma DNA.
Here, we aimed to validate a noninvasive method using capture sequencing for prenatal diagnosis of congenital adrenal hyperplasia due to 21-Hydroxylase deficiency (21-OHD). Noninvasive prenatal diagnosis (NIPD) of 21-OHD was based on 14 plasma samples collected from 12 families, including four plasma sample collected during the first trimester. Targeted capture sequencing was performed using genomic DNA from the parents and child trios to determine the pathogenic and wild-type alleles associated with the haplotypes. Maternal plasma DNA was also sequenced to determine the fetal inheritance of the allele using hidden Markov model-based haplotype linkage analysis. The effect of fetal DNA fraction and sequencing depth on the accuracy of NIPD was investigated. The lower limit of fetal DNA fraction was 2% and the threshold mean sequence depth was 38, suggesting potential advantage if used in early gestation. The CYP21A2 genotype of the fetus was accurately determined in all the 14 plasma samples as early as day 1 and 8 weeks of gestation. Results suggest the accuracy and feasibility of NIPD of 21-OHD using a small target capture region with a low threshold for fetal DNA fraction and sequence depth. Our method is cost-effective and suggests diagnostic applications in clinical practice
Speaker segmentation and clustering
This survey focuses on two challenging speech processing topics, namely: speaker segmentation and speaker clustering. Speaker segmentation aims at finding speaker change points in an audio stream, whereas speaker clustering aims at grouping speech segments based on speaker characteristics. Model-based, metric-based, and hybrid speaker segmentation algorithms are reviewed. Concerning speaker clustering, deterministic and probabilistic algorithms are examined. A comparative assessment of the reviewed algorithms is undertaken, the algorithm advantages and disadvantages are indicated, insight to the algorithms is offered, and deductions as well as recommendations are given. Rich transcription and movie analysis are candidate applications that benefit from combined speaker segmentation and clustering. © 2007 Elsevier B.V. All rights reserved
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