Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

On Pixel-Wise Explanations for Non-Linear Classifier Decisions by Layer-Wise Relevance Propagation.

Abstract: Understanding and interpreting classification decisions of automated image classification systems is of high value in many applications, as it allows to verify the reasoning of the system and provides additional information to the human expert. Although machine learning methods are solving very successfully a plethora of tasks, they have in most cases the disadvantage of acting as a black box, not providing any information about what made them arrive at a particular decision. This work proposes a general solution to the problem of understanding classification decisions by pixel-wise decomposition of nonlinear classifiers. We introduce a methodology that allows to visualize the contributions of single pixels to predictions for kernel-based classifiers over Bag of Words features and for multilayered neural networks. These pixel contributions can be visualized as heatmaps and are provided to a human expert who can intuitively not only verify the validity of the classification decision, but also focus further analysis on regions of potential interest. We evaluate our method for classifiers trained on PASCAL VOC 2009 images, synthetic image data containing geometric shapes, the MNIST handwritten digits data set and for the pre-trained ImageNet model available as part of the Caffe open source package.

Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis

Abstract: Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematop...

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).

MutationTaster2: mutation prediction for the deep-sequencing age

Abstract: To the Editor: The majority of the gene variants discovered by nextgeneration sequencing (NGS) projects are either intronic or synonymous. These variants are difficult to interpret because their effects on protein expression and function tend to be less obvious than those of missense or nonsense variants. Here we present MutationTaster2 (http://www.mutationtaster.org/), the latest version of our web-based software MutationTaster1, which evaluates the pathogenic potential of DNA sequence alterations. It is designed to predict the functional consequences of not only amino acid substitutions but also intronic and synonymous alterations, short insertion and/or deletion (indel) mutations and variants spanning intron-exon borders. MutationTaster2 includes all publicly available single-nucleotide polymorphisms (SNPs) and indels from the 1000 Genomes Project2 (hereafter referred to as 1000G) as well as known disease variants from ClinVar3 and HGMD Public4. Alterations found more than four times in the homozygous state in 1000G or in HapMap5 are automatically regarded as neutral. Variants marked as pathogenic in ClinVar are automatically predicted to be disease causing, and the disease phenotype is displayed. We have integrated tests for regulatory features, including data from the ENCODE project6 and JASPAR7, and score the evolutionary conservation around DNA variants (Supplementary Methods). To reduce the number of false positive splice-site four barcodes left out). We first immobilized cells on glass surfaces (Supplementary Methods). The DNA probes were hybridized, imaged and then removed by DNase I treatment (88.5% ± 11.0% efficiency (± standard deviation); Supplementary Fig. 2 and Supplementary Note). The remaining signal was photobleached (Supplementary Fig. 3). Even after six hybridizations, mRNAs were observed at 70.9% ± 21.8% of the original intensity (Supplementary Fig. 4). We observed that 77.9% ± 5.6% of the spots that colocalized in the first two hybridizations also colocalized with the third hybridization (Fig. 1b and Supplementary Figs. 5 and 6). We quantified the mRNA abundances by counting the occurrence of corresponding barcodes in the cell (n = 37 cells; Supplementary Figs. 7 and 8). We also show that mRNAs can be stripped and rehybridized efficiently in adherent mammalian cells (Supplementary Figs. 9 and 10). Sequential barcoding has many advantages. First, it scales up quickly; with even two dyes the coding capacity is in principle unlimited. Second, during each hybridization, all available FISH probes against a transcript can be used, thereby increasing the brightness of the FISH signal. Last, barcode readout is robust, enabling full z stacks on native samples. This barcoding scheme is conceptually akin to sequencing transcripts in single cells with FISH. In contrast with the technique used by Ke et al.2, our method takes advantage of the high hybridization efficiency of FISH (>95% of the mRNAs are detected1,3) and the fact that base-pair resolution is usually not needed to uniquely identify a transcript. We note that FISH probes can also be designed to resolve a large number of splice isoforms and single-nucleotide polymorphisms3, as well as chromosome loci4, in single cells. In combination with our previous report of super-resolution FISH1, the sequential barcoding method will enable the transcriptome to be directly imaged at single-cell resolution in complex samples such as brain tissue.