GlycoNote with Iterative Decoy Searching and Open-Search Component Analysis for High-Throughput and Reliable Glycan Spectral Interpretation.

Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.

Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease.

The first reported outbreak of an undetermined species of human infection with spotted fever group Rickettsia in Lu'an, China.

OBJECTIVE: On May 2, 2017, an outbreak of unexplained fever with rashes was reported in Lu'an, China. In this study, we aimed to identify the possible pathogens, epidemiological characteristics, and risk factors of this outbreak. METHODS: We conducted descriptive field epidemiological studies. Blood samples were tested using an indirect immunofluorescence assay for Rickettsia rickettsii antibody, and nested polymerase chain reaction and gene sequencing assays were performed. RESULTS: We recruited 39 cases who had symptomatic onset from April 20 to June 8, 2017. Among these, 9 were suspected cases, 18 were probable cases, and 12 were confirmed cases. No one died. The main clinical manifestations were fever (100%), rash (100%), fatigue (97.3%), myalgia (83.8%), and anorexia (83.8%). None of the patients died. Thirty-seven patients who were treated with antibiotics during hospitalization showed significant improvement. The cases were distributed across 14 townships in 2 counties. The median age was 59 (43.0-81.0) years, of which 93.3% had a history of tea picking (28/30), and 77.3% (17/22) had a history of tick bites. The mean incubation period was 5.0 days (2.0-13.0 days). Serum IgG titers were higher in convalescent patients than in the general population (p = 0.016). Phylogenetic analysis revealed that the ompA sequences of Rickettsia sp. Lu'an-2018 had an 86.8%-99.0% sequence identity with the 23 strains of Rickettsia found worldwide. CONCLUSIONS: This was the first reported outbreak of an undetermined species of a human infection with the spotted fever group of Rickettsia in China, which might be caused by ticks biting local residents when picking tea.