We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

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Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find therapeutic leads for this subgroup, we analyzed 58 blastemal type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large replication cohort. Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of blastemal cases); mutations in the DROSHA/DGCR8 microprocessor genes (18.2% of blastemal cases); mutations in DICER1 and DIS3L2; and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations strongly altered miRNA expression patterns in tumors, which was functionally validated in cell lines expressing mutant DROSHA.

Biotrophic fungal plant pathogens establish an intimate relationship with their host to support the infection process. Central to this strategy is the secretion of a range of protein effectors that enable the pathogen to evade plant immune defences and modulate host metabolism to meet its needs. In this Review, using the smut fungus Ustilago maydis as an example, we discuss new insights into the effector repertoire of smut fungi that have been gained from comparative genomics and discuss the molecular mechanisms by which U. maydis effectors change processes in the plant host. Finally, we examine how the expression of effector genes and effector secretion are coordinated with fungal development in the host.

Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players.

Supplementary data are available at Bioinformatics online.

BackgroundWe present the first sequencing data using the combinatorial probe-anchor synthesis (cPAS)-based BGISEQ-500 sequencer. Applying cPAS, we investigated the repertoire of human small non-coding RNAs and compared it to other techniques.ResultsStarting with repeated measurements of different specimens including solid tissues (brain and heart) and blood, we generated a median of 30.1 million reads per sample. 24.1 million mapped to the human genome and 23.3 million to the miRBase. Among six technical replicates of brain samples, we observed a median correlation of 0.98. Comparing BGISEQ-500 to HiSeq, we calculated a correlation of 0.75. The comparability to microarrays was similar for both BGISEQ-500 and HiSeq with the first one showing a correlation of 0.58 and the latter one correlation of 0.6. As for a potential bias in the detected expression distribution in blood cells, 98.6% of HiSeq reads versus 93.1% of BGISEQ-500 reads match to the 10 miRNAs with highest read count. After using miRDeep2 and employing stringent selection criteria for predicting new miRNAs, we detected 74 high-likely candidates in the cPAS sequencing reads prevalent in solid tissues and 36 candidates prevalent in blood.ConclusionsWhile there is apparently no ideal platform for all challenges of miRNome analyses, cPAS shows high technical reproducibility and supplements the hitherto available platforms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0287-1) contains supplementary material, which is available to authorized users.

There are numerous studies on the immune response against malignant human tumors. This study was aimed to address the complexity and specificity of humoral immune response against a benign human tumor. We assembled a panel of 62 meningiomaexpressed antigens that show reactivity with serum antibodies of meningioma patients, including 41 previously uncharacterized antigens by screening of a fetal brain expression library. We tested the panel for reactivity with 48 sera, including sera of patients with common-type, atypical, and anaplastic meningioma, respectively. Meningioma sera detected an average of 14.6 antigens per serum and normal sera an average of 7.8 antigens per serum (P ‫؍‬ 0.0001). We found a decline of seroreactivity with malignancy with a statistical significant difference between common-type and anaplastic meningioma (P < 0.05). We detected 17 antigens exclusively with patient sera, including 12 sera that were reactive against KIAA1344, 9 against natural killer tumor recognition (NKTR), and 7 against SRY (sex determining region Y)-box2 (SOX2). More than 80% of meningioma patients had antibodies against at least one of the antigens KIAA1344, SC65, SOX2, and C6orf153. Our results show a highly complex but specific humoral immune response against a benign tumor with a distinct serum reactivity pattern and a decline of complexity with malignancy. The frequent antibody response against specific antigens offers new diagnostic and therapeutic targets for meningioma. We developed a statistical learning method to differentiate sera of meningioma patients from sera of healthy donors. meningioma