Interspliced transcription chimeras: Neglected pathological mechanism infiltrating gene accession queries?

AbstractOver half of the DNA of mammalian genomes is transcribed, and one of the emerging enigmas in the field of RNA research is intergenic splicing or transcription induced chimerism. We argue that fused low-copy-number transcripts constitute neglected pathological mechanism akin to copy number variation, due to loss of stoichiometric subunit ratios in protein complexes. An obstacle for transcriptomics meta-analysis of published microarrays is the traditional nomenclature of merged transcript neighbors under same accession codes. Tandem transcripts cover 4–20% of genomes but are only loosely overlapping in population. They were most enriched in systems medicine annotations concerning neurology, thalassemia and genital disorders in the GeneGo Inc. MetaCore-MetaDrugTM knowledgebase, evaluated with external randomizations here. Clinical transcriptomics is good news since new disease etiologies offer new remedies. We identified homeotic HOX-transfactors centered around BMI-1, the Grb2 adaptor network, the kallikrein system, and thalassemia RNA surveillance as vulnerable hotspot chimeras. As a cure, RNA interference would require verification of chimerism from symptomatic tissue contra healthy control tissue from the same patient

Robust extraction of functional signals from gene set analysis using a generalized threshold free scoring function

Peer reviewe

Acyl chain-dependent effect of lysophosphatidylcholine on endothelial prostacyclin production

Peer reviewe

Multi-scale Gaussian representation and outline-learning based cell image segmentation

BACKGROUND: High-throughput genome-wide screening to study gene-specific functions, e.g. for drug discovery, demands fast automated image analysis methods to assist in unraveling the full potential of such studies. Image segmentation is typically at the forefront of such analysis as the performance of the subsequent steps, for example, cell classification, cell tracking etc., often relies on the results of segmentation. METHODS: We present a cell cytoplasm segmentation framework which first separates cell cytoplasm from image background using novel approach of image enhancement and coefficient of variation of multi-scale Gaussian scale-space representation. A novel outline-learning based classification method is developed using regularized logistic regression with embedded feature selection which classifies image pixels as outline/non-outline to give cytoplasm outlines. Refinement of the detected outlines to separate cells from each other is performed in a post-processing step where the nuclei segmentation is used as contextual information. RESULTS AND CONCLUSIONS: We evaluate the proposed segmentation methodology using two challenging test cases, presenting images with completely different characteristics, with cells of varying size, shape, texture and degrees of overlap. The feature selection and classification framework for outline detection produces very simple sparse models which use only a small subset of the large, generic feature set, that is, only 7 and 5 features for the two cases. Quantitative comparison of the results for the two test cases against state-of-the-art methods show that our methodology outperforms them with an increase of 4-9% in segmentation accuracy with maximum accuracy of 93%. Finally, the results obtained for diverse datasets demonstrate that our framework not only produces accurate segmentation but also generalizes well to different segmentation tasks

Reassigning the shapes of the 0(+) states in the Pb-186 nucleus

Across the physics disciplines, the 186Pb nucleus is the only known system, where the two first excited states, together with the ground state, form a triplet of zero-spin states assigned with prolate, oblate and spherical shapes. Here we report on a precision measurement where the properties of collective transitions in 186Pb were determined in a simultaneous in-beam γ-ray and electron spectroscopy experiment employing the recoil-decay tagging technique. The feeding of the 02+ state and the interband 22+→21+ transition have been observed. We also present direct measurement of the energies of the electric monopole transitions from the excited 0+ states to the 0+ ground state. In contrast to the earlier understanding, the obtained reduced transition probability B(E2;21+→02+) value of 190(80) W.u., the transitional quadrupole moment ∣Qt(21+→02+)∣=7.7(33) eb and intensity balance arguments provide evidence to reassign the 02+ and 03+ states with predominantly prolate and oblate shape, respectively. Our work demonstrates a step-up in experimental sensitivity and paves the way for systematic studies of electric monopole transitions in this region. These electric monopole transitions probe the nuclear volume in a unique manner and provide unexploited input for development of the next-generation energy density functional models