34 research outputs found
Approximate Profile Maximum Likelihood
We propose an efficient algorithm for approximate computation of the profile
maximum likelihood (PML), a variant of maximum likelihood maximizing the
probability of observing a sufficient statistic rather than the empirical
sample. The PML has appealing theoretical properties, but is difficult to
compute exactly. Inspired by observations gleaned from exactly solvable cases,
we look for an approximate PML solution, which, intuitively, clumps comparably
frequent symbols into one symbol. This amounts to lower-bounding a certain
matrix permanent by summing over a subgroup of the symmetric group rather than
the whole group during the computation. We extensively experiment with the
approximate solution, and find the empirical performance of our approach is
competitive and sometimes significantly better than state-of-the-art
performance for various estimation problems
Frequency and Variability of Genomic Rearrangements on <i>MSH2</i> in Spanish Lynch Syndrome Families
<div><p>Large genomic rearrangements (LGRs) in DNA-mismatch-repair (MMR) genes, particularly among <i>MSH2</i> gene, are frequently involved in the etiology of Lynch syndrome (LS). The Multiplex Ligation and Probe Amplification assay (MLPA) is commonly used to identify such alterations. However, in most cases, the MLPA-identified alteration is not characterized at the molecular level, which might be important to identify recurrent alterations and to analyze the molecular mechanisms underlying these mutational events. Probands from a cohort of Lynch Syndrome families were screened for point mutation in MMR genes, subsequently the MLPA assay was used for LGR screening. The identified MLPA alteration was confirmed by cDNA, CGH-microarrays or massive parallel sequencing. In this study, we have delimited the region of 11 LGRs variants on <i>MSH2</i> locus. Six of them were fully characterized the breakpoints and 9 of them were considered pathogenic. According to our data, LGR on <i>MSH2</i> locus constituted the 10.8% (9 out of 83) of pathogenic germline alterations found in LS. The frequency of colorectal cancer (CRC) and endometrial cancer (EC) in LGR carriers was 55% and 11% respectively. Analysis of the breakpoint sequences revealed that in 3 cases, deletions appeared to originate from Alu-mediated recombination events. In the remaining cases, sequence alignment failed to detect microhomology around the breakpoints. The present study provides knowledge on the molecular characterization of <i>MSH2</i> LGRs, which may have important implications in LS diagnosis and Genetic Counseling. In addition, our data suggests that nonhomologous events would be more frequently involved in the etiology of <i>MSH2</i> LGRs than expected.</p></div
Gene amplification of exons 8–10.
<p><b>A</b>) array CGH rearrangement characterization. <b>B</b>) Amplification of the junction fragment using the outward facing primers in duplicated head-to-tail interval and electrophoresis gel showing PCR product in a mutation carrier. <b>C</b>) Sequence electropherogram of the junction fragment.</p
Genotype-phenotype correlation in MSH2 mutation carriers.
<p>Genotype-phenotype correlation in MSH2 mutation carriers.</p
Clinical and molecular characteristics of mutation carriers.
a<p>Nomenclature based on mRNA sequence with GenBank Accession Code NM_002354.2.</p>b<p>Nomenclature according to ISCN (2009).</p><p>Abbreviations:Family ID, family identification; Ped ID, pedigree Identification; AMS, Amsterdam criteria; CRC, colorectal cancer; EC, Endometrial cancer; UC, Urothilial cancer; A, Villous Adenoma; MLPA, Multiplex ligation-dependent probe amplification; MPS, Massive Parallel Sequencing.</p
Additional file 2: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer
Absolute and average relative counts of reads mapped to each ncRNAs biotype per sample and fraction. (XLSX 15 kb
Role of <i>GALNT12</i> in the genetic predisposition to attenuated adenomatous polyposis syndrome
<div><p>The involvement of <i>GALNT12</i> in colorectal carcinogenesis has been demonstrated but it is not clear to what extent it is implicated in familial CRC susceptibility. Partially inactivating variant, NM_024642.4:c.907G>A, p.(D303N), has been previously detected in familial CRC and proposed as the causative risk allele. Since phenotypes of the described carrier families showed not only CRC but also a polyp history, we hypothesized that <i>GALNT12</i> could be involved in adenoma predisposition and consequently, in hereditary polyposis CRC syndromes. For that purpose, we have screened the <i>GALNT12</i> gene in germline DNA from 183 unrelated attenuated polyposis patients. c.907G>A, p.(D303N) was detected in 4 cases (MAF = 1.1%) and no other candidate variants were found. After segregation studies, LOH analyses, glycosylation pattern tests and case-control studies, our results did not support the role of c.907G>A, p.(D303N) as a high-penetrance risk allele for polyposis CRC.</p></div
Additional file 5: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer
Excel file with two documents summarizing the results obtained from the differential expression NF-CELL versus NF-EXO analyses for differentially distributed lncRNAs and sncRNAs. (XLSX 73 kb
Additional file 7: of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer
Mini web site presenting a dynamic venn diagram intersecting the relationships of significance from the assayed ncRNAs in the differential expression analyses performed between NF- and CAF- exosomes versus their respective cellular environments (i.e. NF-CELL versus NF-EXO and CAF-CELL versus CAF-EXO). Clicking on any intersected number, the web site opens a dialog summarizing the ncRNAs species that correspond to the intersection. (HTML 120 kb
Additional file 13 of Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer
: Multiple alignment of the 42 sncRNAs over represented in CAF-EXO samples. (FASTA 8 kb