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

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

Pedigrees of families harboring c.907G>A (p.D303N) and segregation analysis.

<p>Probands are marked with arrows. MUT = individual carrying the c.907G>A (p.D303N) allele. WT = individual not carrying the c.907G>A, p.(D303N) allele. CRC = colorectal cancer. y = age at diagnosis or age at the time of DNA extraction (in healthy subjects).</p

c.907G>A, p.(D303N) allelic population frequencies and association analysis.

<p>c.907G>A, p.(D303N) allelic population frequencies and association analysis.</p

Clinicopathological characteristics of study cohorts.

<p>Clinicopathological characteristics of study cohorts.</p

Adenomas tested for LOH and MUC1 IHC.

<p>Adenomas tested for LOH and MUC1 IHC.</p

List of CRC predisposition genes included in the NGS custom panel.

<p>List of CRC predisposition genes included in the NGS custom panel.</p

Clinical characteristics of c.907G>A, p.(D303N) carriers.

<p>Clinical characteristics of c.907G>A, p.(D303N) carriers.</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

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