HPLC-LIF for early detection of oral cancer

At present, the diagnosis of many cancers relies on the subjective interpretation of morphological changes in biopsy samples. This usually provides only late diagnosis. Early detection, which can provide more successful therapy, is expected to be possible by identification of tumour markers in physiological samples. Immunoassay used at present for this purpose has several drawbacks. It is applicable only for known markers, can usually detect only one marker at a time, and may also fail to detect a marker when there exist conditions, which may mask or prevent the interaction between antigen and the antibody. We have developed a high performance liquid chromatography- laser induced fluorescence (HPLC-LIF) technique to detect and record simultaneously spectra and chromatograms of physiological samples, which will enable the detection of multiple 'markers' in a single physiological sample in a short time. Samples of saliva and serum from normal and oral cancer subjects have been studied with the set up. The present studies show that body fluids like saliva and serum of normal, premalignant and malignant subjects have substantially different protein profiles. By simultaneous recording of the chromatographic peaks and corresponding fluorescence spectra, it is possible to carry out unambiguous discrimination between normal, premalignant and malignant cases even when markers are present in femto/subfemtomole quantities, which should assist in early diagnosis of neoplasia

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

HPLC-LIF of serum for early detection of oral cancer

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Protein profiles in oral premalignancies: a laser spectroscopy study

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Mycobacterium avium in Community and Household Water, Suburban Philadelphia, Pennsylvania, USA, 2010–2012

Attention to environmental sources of Mycobacterium avium complex (MAC) infection is a vital component of disease prevention and control. We investigated MAC colonization of household plumbing in suburban Philadelphia, Pennsylvania, USA. We used variable-number tandem-repeat genotyping and whole-genome sequencing with core genome single-nucleotide variant analysis to compare M. avium from household plumbing biofilms with M. avium isolates from patient respiratory specimens. M. avium was recovered from 30 (81.1%) of 37 households, including 19 (90.5%) of 21 M. avium patient households. For 11 (52.4%) of 21 patients with M. avium disease, isolates recovered from their respiratory and household samples were of the same genotype. Within the same community, 18 (85.7%) of 21 M. avium respiratory isolates genotypically matched household plumbing isolates. Six predominant genotypes were recovered across multiple households and respiratory specimens. M. avium colonizing municipal water and household plumbing may be a substantial source of MAC pulmonary infection

Plasma extracellular vesicle proteins as promising noninvasive biomarkers for diagnosis of idiopathic pulmonary fibrosis

Abstract High‐resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five‐protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five‐protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819–1.011) and 0.958 (95%CI: 0.882–1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility

Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products

ISSN:1552-4450ISSN:1552-446