354 research outputs found
Feature Selection in k-Median Clustering
An e ective method for selecting features in clustering
unlabeled data is proposed based on changing the objective
function of the standard k-median clustering algorithm. The
change consists of perturbing the objective function by a
term that drives the medians of each of the k clusters toward
the (shifted) global median of zero for the entire dataset.
As the perturbation parameter is increased, more and more
features are driven automatically toward the global zero
median and are eliminated from the problem until one last
feature remains. An error curve for unlabeled data clustering
as a function of the number of features used gives reducedfeature
clustering error relative to the \gold standard" of the
full-feature clustering. This clustering error curve parallels
a classi cation error curve based on real data labels. This
justi es the utility of the former error curve for unlabeled
data as a means of choosing an appropriate number of
reduced features in order to achieve a correctness comparable
to that obtained by the full set of original features. For
example, on the 3-class Wine dataset, clustering with 4
selected input space features is comparable to within 4%
to clustering using the original 13 features of the problem
Modeling and visualizing uncertainty in gene expression clusters using Dirichlet process mixtures
Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data, little attention has been paid to uncertainty in the results obtained. Dirichlet process mixture (DPM) models provide a nonparametric Bayesian alternative to the bootstrap approach to modeling uncertainty in gene expression clustering. Most previously published applications of Bayesian model-based clustering methods have been to short time series data. In this paper, we present a case study of the application of nonparametric Bayesian clustering methods to the clustering of high-dimensional nontime series gene expression data using full Gaussian covariances. We use the probability that two genes belong to the same cluster in a DPM model as a measure of the similarity of these gene expression profiles. Conversely, this probability can be used to define a dissimilarity measure, which, for the purposes of visualization, can be input to one of the standard linkage algorithms used for hierarchical clustering. Biologically plausible results are obtained from the Rosetta compendium of expression profiles which extend previously published cluster analyses of this data
Huntington’s disease Clinical Trials Corner: February 2018
© 2018 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0)In the second edition of the Huntington’s Disease Clinical Trials Corner we list all currently registered and ongoing clinical trials, summarise the top-line results of the recently-announced IONIS-HTTRX trial (NCT02519036), expand on Wave Life Sciences’ PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846), and cover one recently finished trial: the FIRST-HD deutetrabenazine trial (NCT01795859).info:eu-repo/semantics/publishedVersio
Clinical trials corner: September 2017
© 2017 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0).Clinical Trials Corner of Journal of Huntington’s Disease will regularly review ongoing and recently completed clinical trials in Huntington’s disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx, and cover two recently finished trials: Amaryllis and Pride-HD.info:eu-repo/semantics/publishedVersio
Huntington's Disease Clinical Trials Corner: November 2022
In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the PIVOT HD (PTC518), and SIGNAL (pepinemab) trials, and list all currently registered and ongoing clinical trials in Huntington's disease.We also introduce a 'breaking news' section highlighting recent updates about the SELECT HD, uniQure AMT-130, and VIBRANT HD clinical trials
Huntington's Disease Clinical Trials Corner: July 2023
In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the GENERATION HD2 (tominersen) and on the Asklepios Biopharmaceutical/BrainVectis trial with AB-1001. We also comment on the recent findings from the PROOF-HD trial, and list all currently registered and ongoing clinical trials in Huntington's disease
Huntington's disease clinical trials corner: April 2022
In this edition of the Huntington's Disease Clinical Trials Corner we expand on GENERATION HD1, PRECISION-HD1 and PRECISION-HD2, SELECT-HD, and VIBRANT-HD trials, and list all currently registered and ongoing clinical trials in Huntington's disease
Tetrabenazine versus deutetrabenazine for Huntington's disease : twins or distant cousins?
© 2017 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background:
Tetrabenazine is the only US Food and Drug Administration‐approved drug for Huntington's disease, and deutetrabenazine was recently tested against placebo. A switching‐trial from tetrabenazine to deutetrabenazine is underway, but no head‐to‐head, blinded, randomized controlled trial is planned. Using meta‐analytical methodology, the authors compared these molecules.
Methods:
RCTs comparing tetrabenazine or deutetrabenazine with placebo in Huntington's disease were searched. The authors assessed the Cochrane risk‐of‐bias tool, calculated indirect treatment comparisons, and applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.
Results:
The evidence network for this report comprised 1 tetrabenazine trial and 1 deutetrabenazine trial, both against placebo. Risk of bias was moderate in both. Participants in the tetrabenazine and deutetrabenazine trials did not differ significantly on motor scores or adverse events. Depression and somnolence scales significantly favored deutetrabenazine.
Conclusion:
There is low‐quality evidence that tetrabenazine and deutetrabenazine do not differ in efficacy or safety. It is important to note that these results are likely to remain the only head‐to‐head comparison between these 2 compounds in Huntington's disease.info:eu-repo/semantics/publishedVersio
Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.
Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously
JAK/STAT Signalling in Huntington's Disease Immune Cells.
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral innate immune activation have been described as features of the disease. Isolated human HD monocytes have been shown to produce more cytokines upon LPS stimulation compared to control monocytes. Understanding alterations in the signalling cascades responsible and activated by this increase in pro-inflammatory cytokine production is crucial in understanding the molecular basis of this phenomenon. Here we investigated the signalling cascade most commonly activated by pro-inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow cytometry, we show that one out of three key transcription factors activated by JAK/STAT signalling is altered in primary human HD innate immune cells, suggesting that this pathway may only play a minor, additive role in the immune cell dysfunction in HD
- …