Project description:Chromatin loops are a major componant of 3D nuclear organization that appear as intense point-to-point interactions in Hi-C maps. Identification of these loops is an important part of Hi-C analysis. We present SIP, Significant Interaction Peak caller, a platform independent program to identify these loops in a time and memory efficient manner and which is resistant to noise and sequencing depth. We also present a companion tool, SIPMeta, to create more visually accurate average plots of Hi-C and HiChIP data. We then demonstrate that use of SIP and SIPMeta can lead to biological insight through characterizing the contribution of several transcription factors to CTCF loops in human cells. We then use SIP and SIPMeta to discover loops associated with condensin IDCC in C. elegans and confirm these loops by HiChIP. These loops form a network of interactions and likely explain the partial condensation of dosage compensated X chromosomes in hermaphrodites.

2020-02-04 | GSE132640 | GEO

SNP-based mapping and gene expression profiling identifies novel chromosomal imbalances and candidate genes in T-PLL

Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive lymphoma derived from mature T cells, which is, in most cases, characterized by the presence of an inv(14)(q11q32)/t(14;14)(q11;q32) and a characteristic pattern of secondary chromosomal aberrations. DNA microarray technology was employed to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor-derived peripheral blood cell samples, with five highly purified inv(14)/t(14;14)-positive T-PLL blood samples. Between the two experimental groups, 734 genes were identified as differentially expressed, including functionally important genes involved in lymphomagenesis, cell cycle regulation, apoptosis and DNA repair. Notably, the differentially expressed genes were found to be significantly enriched in genomic regions affected by recurrent chromosomal imbalances. Upregulated genes clustered on chromosome arms 6p and 8q, and downregulated genes on 6q, 8p, 10p, 11q and 18p. High-resolution copy-number determination using single nucleotide polymorphism chip technology in 11 inv(14)/t(14;14)-positive T-PLL and 1 without the inv(14) including those analyzed for gene expression, refined chromosomal breakpoints as well as regions of imbalances. In conclusion, combined transcriptional and molecular cytogenetic profiling identified novel specific chromosomal loci and genes that are likely to be involved in disease progression and suggests a gene dosage effect as a pathogenic mechanism in T-PLL. Each Sample has its raw data file linked as a supplementary file. Keywords: disease state analysis

2008-02-07 | GSE10387 | GEO

Next generation sequencing of small non-coding RNAs of T-PLL patients and normal T-cell fractions

Project description:T cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small to medium sized pro-lymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide-range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and genotypic subgroups that may explain the heterogeneity of the disease. We found that T-PLL does not show a clear skewing in T cell receptor alpha (TRA), TRB gene usage and CDR3 stereotypy. In addition, multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups. However, based on miRNA expression profiles, T-PLL samples did clearly cluster in subgroups. We identified 35 miRNAs that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR-200c/141 expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 in T-PLL correlated with downregulation of their targets ZEB2 and TGFβR3, indicating that the TGFβ pathway is affected. Our results thus highlight the emerging role for aberrantly expressed oncogenic miRNAs in T-PLL, thereby paving the way for new therapeutic targets in this disease.

2021-04-02 | GSE147932 | GEO