Paper accepted for Oral Presentation at PRNI 2015

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May 062015
 

Our paper with the title “Joint Feature Extraction from Functional Connectivity Graphs with Multi-task Feature Learning” was selected for oral presentation at PRNI 2015 (Stanford, USA in June 2015).

Abstract:

Using sparse regularization in classifier learning is an appealing strategy to locate relevant brain regions and connections between regions within high-dimensional brain imaging data. A major drawback of sparse classifier learning is the lack of stability to data perturbations, which leads to different sets of features being selected. Here, we propose to use multi-task feature learning (MFL) to generate sparse and stable classifiers. In classification experiments on functional connectivity estimated from resting state functional magnetic resonance imaging (fMRI), we show that MFL more consistently selects the same connections across bootstrap samples and provides more interpretable models in multiclass settings than standard sparse classifiers, while achieving similar classification performance.

 Posted by at 06:24

New book “Applied Neurogenomics” published!

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Jan 142015
 

Applied Neurogenomics “contains detailed methods relevant to the genomics of neurodegenerative diseases, particularly Alzheimer’s disease and Huntington’s disease”

The book contains on chapter on targeted re-sequencing of genes written by Peter Weber and myself. The chapter can be accessed directly here.

Here is the abstract:

The method presented here enables researchers to sequence a target region in the genome in a large number of subjects at comparatively low cost. The method relies heavily on modern massively parallel sequencing (MPS) technologies, and the costs and workload for DNA sample preparation are major factors in targeted re-sequencing studies involving many individual samples. In order to reduce costs during sample preparation, we propose to sequence pools of subjects rather than individual subjects. Thus, our approach is divided into four subparts: (1) non-barcoded sample pooling, (2) enrichment of the target region, (3) sequencing using standard MPS protocols, and (4) tailored bioinformatics analysis of the data, which identifies rare variants in the pools.

 Posted by at 20:59

Paper accepted in Endocrinology!

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Apr 182014
 

Our paper entitled “A polymorphism in the crhr1 gene determines stress vulnerability in male mice” has been accepted by Endocrinology!

Abstract:
Chronic stress is a risk factor for psychiatric disorders but does not necessarily lead to uniform longterm effects on mental health, suggesting modulating factors such as genetic predispositions. Here we address the question whether natural genetic variations in the mouse corticotropin releasing hormone receptor 1 (crhr1) locus modulate the effects of adolescent chronic social stress (ACSS) on long-term stress hormone dysregulation in outbred CD1 mice, which allows us a better understanding of the currently reported GxE interactions of early trauma and crhr1 in humans. We identified an intronic genetic variant in the mouse crhr1 locus, rs27040842, that modulates the long-term effects of ACSS on basal hypothalamic-pituitary-adrenal axis activity. This effect is likely mediated by higher levels of CRHR1, as crhr1 mRNA expression and CRHR1 receptor binding was enhanced in these animals. Furthermore, a CRHR1 receptor antagonist normalized these long-term effects. Deep-sequencing of the crhr1 locus in CD1 mice revealed a large number of linked variants with some located in important regulatory regions, similar to the location of human crhr1 variants implicated in modulating GxE interactions. Our data support that the described gene x stress exposure interaction in this animal model is based on naturally occurring genetic variations in the crhr1 gene associated with enhanced CRHR1 mediated signaling. Our results suggest that patients with a specific genetic predisposition in the crhr1 gene together with an exposure to chronic stress may benefit from a treatment selectively antagonizing CRHR1 hyperactivity.

 Posted by at 19:03

Paper published in Annals of Neurology

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Apr 152014
 

Our paper was published in Annals of Neurology!

Click here for Stanford’s Press release.

Title: Sex modifies the APOE-related risk of developing Alzheimer disease

Abstract:

Objective
The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case–control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels.

Methods
Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer’s Disease Neuroimaging Initiative.

Results
Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women).

Interpretation
APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis

 Posted by at 08:26

ReAnnotator online at SourceForge

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Nov 172013
 

The microarray technology is an established approach for high throughput gene expression analysis. An accurate mapping between array probes and the genes that they are targeting is essential for generating accurate biological findings. The manufacturers typically provide such annotation tables. However, these tables rely on older genome and transcriptome versions that differ substantially from the current state-of-the-art sequence databases.

Re-Annotator is a re-annotation pipeline for gene expression microarrays that will bring probe annotations up-to-date! The software is available at the Software page or here at directly at SourceForge.

 Posted by at 05:01

Paper accepted in “Brain Imaging and Behavior”!

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Oct 232013
 

Our paper with the title “Apolipoprotein E, Gender, and Alzheimer’s Disease: An Overlooked, but Potent and Promising Interaction” was accepted for publication in Brain Imaging and Behavior. The paper is a review on the current literature regarding a gender by genotype (ApoE) interaction in Alzheimer’s disease.

“Alzheimer’s disease (AD) is an increasingly prevalent, fatal neurodegenerative disease that has proven resistant, thus far, to all attempts to prevent it, forestall it, or slow its progression. The ε4 allele of the Apolipoprotein E gene (APOE4) is a potent genetic risk factor for sporadic and late-onset familial AD. While the link between APOE4 and AD is strong, many expected effects, like increasing the risk of conversion from MCI to AD, have not been widely replicable. One critical, and commonly overlooked, feature of the APOE4 link to AD is that several lines of evidence suggest it is far more pronounced in women than in men. Here we review previous literature on the APOE4 by gender interaction with a particular focus on imaging-related studies.”

Authors: Leo Unger, Andre Altmann, Michael Greicius

 

 Posted by at 17:48

New Website Online

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Jul 122011
 

The site is still work in progress. But already by far more appealing than my old one.

 Posted by at 23:36