pParse: a method for accurate determination of monoisotopic peaks in high-resolution mass spectra.

Determining the monoisotopic peak of a precursor is a first step in interpreting mass spectra, which is basic but non-trivial. The reason is that in the isolation window of a precursor, other peaks interfere with the determination of the monoisotopic peak, leading to wrong mass-to-charge ratio or charge state. Here we propose a method, named pParse, to export the most probable monoisotopic peaks for precursors, including co-eluted precursors. We use the relationship between the position of the highest peak and the mass of the first peak to detect candidate clusters. Then, we extract three features to sort the candidate clusters: (i) the sum of the intensity, (ii) the similarity of the experimental and the theoretical isotopic distribution, and (iii) the similarity of elution profiles. We showed that the recall of pParse, MaxQuant, and BioWorks was 98-98.8%, 0.5-17%, and 1.8-36.5% at the same precision, respectively. About 50% of tandem mass spectra are triggered by multiple precursors which are difficult to identify. Then we design a new scoring function to identify the co-eluted precursors. About 26% of all identified peptides were exclusively from co-eluted peptides. Therefore, accurately determining monoisotopic peaks, including co-eluted precursors, can greatly increase peptide identification rate.

Global White Matter Hypoperfusion on CT Predicts Larger Infarcts and Hemorrhagic Transformation after Acute Ischemia.

INTRODUCTION: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased risk of hemorrhagic transformation (HT) after thrombolysis. AIM: We sought to determine whether white matter hypoperfusion (WMHP) on perfusion CT (CTP) was related to WMH, and if WMHP predisposed to acute lacunar stroke subtype and HT after thrombolysis. METHODS: Acute ischemic stroke patients within 12 h of symptom onset at 2 centers were prospectively recruited between 2011 and 2013 for the International Stroke Perfusion Imaging Registry. Participants routinely underwent baseline CT imaging, including CTP, and follow-up imaging with MRI at 24 h. RESULTS: Of 229 ischemic stroke patients, 108 were Caucasians and 121 Chinese. In the contralateral white matter, patients with acute lacunar stroke had lower cerebral blood flow (CBF) and cerebral blood volume (CBV), compared to those with other stroke subtypes (P = 0.041). There were 46 patients with HT, and WMHP was associated with increased risk of HT (R(2) = 0.417, P = 0.002). Compared to previously reported predictors of HT, WMHP performed better than infarct core volume (R(2) = 0.341, P = 0.034), very low CBV volume (R(2) = 0.249, P = 0.026), and severely delayed perfusion (Tmax>14 second R(2) = 0.372, P = 0.011). Patients with WMHP also had larger acute infarcts and increased infarct growth compared to those without WMHP (mean 28 mL vs. 13 mL P < 0.001). CONCLUSION: White matter hypoperfusion remote to the acutely ischemic region on CTP is a marker of small vessel disease and was associated with increased HT, larger acute infarct cores, and greater infarct growth.

Preprocessing of tandem mass spectrometric data based on decision tree classification.

In this study, we present a preprocessing method for quadrupole time-of-flight (Q-TOF) tandem mass spectra to increase the accuracy of database searching for peptide (protein) identification. Based on the natural isotopic information inherent in tandem mass spectra, we construct a decision tree after feature selection to classify the noise and ion peaks in tandem spectra. Furthermore, we recognize overlapping peaks to find the monoisotopic masses of ions for the following identification process. The experimental results show that this preprocessing method increases the search speed and the reliability of peptide identification.

Early expression of mannose-binding lectin 2 during Aspergillus fumigatus infection in human corneal epithelial cells.

AIM: To evaluate the early expression of mannose-binding lectin 2 (MBL2) in human corneal epithelial cells (HCECs) infected by Aspergillus fumigatus (AF). METHODS: HCECs cultured in vitro with AF antigens and sampled at 0, 0.5, 1, 2, 4, 6 and 8h. The expression of MBL2 mRNA was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of MBL2 protein in supernatant fluid was shown by enzyme linked immunosorbent assay (ELISA). MBL2 protein in HCECs was detected by immunocytochemistry at 0 and 24h. RESULTS: MBL2 mRNA and protein are expressed in normal HCECs. The expression of MBL2 mRNA and protein in supernatant fluid begin to increase after being stimulated with AF antigens. The most significantly peak of MBL2 mRNA is in 2h. The protein of MBL2 in supernatant fluid decrease gradually after 0.5h. The protein in HCECs expression increase after stimulation of 24h. CONCLUSION: MBL2 receptor expressed in normal HCECs in vitro. The stimulation by AF antigens can increase the early expression of it.

Design of the CHina Epidemiology Research in Subarachnoid Haemorrhage (CHERISH) study.

RATIONALE: Limited epidemiological data exist on subarachnoid haemorrhage (SAH) in China. Effective prevention requires knowledge of the rates and risk factors for SAH the most lethal type of stroke that most often affects younger adults. We report the methods and the initial experience of a new study to address this deficiency. AIMS: To determine the incidence, risk factors, management and outcomes of SAH. DESIGN: The CHina Epidemiology Research In Subarachnoid Haemorrhage (CHERISH) is a prospective, population-based, case-control study in a defined region (study population 1.7 million) of the city of Baotou in Inner Mongolia, China. METHODS: Cases of spontaneous SAH are identified using standard definitions through prospective surveillance of all major acute care hospitals with neurology/neurosurgery facilities, small hospitals/clinics, and the single city crematorium over a 2-year period. Verbal autopsy procedures are used to ascertain the probable causes of deaths outside of hospital. For each case, two nonrelative controls without SAH are matched by age (5-year strata), gender, and district of residence. Data are collected on socio-demography, lifestyle factors, and medical history, and blood is taken for the extraction and storage of DNA. Details of the clinical features, presentation, and management of SAH are obtained from cases, and survivors provide details on health care utilisation, physical function, health-related quality of life, and complications, at 6-months. STUDY OUTCOMES: The primary outcomes are overall, age- and gender-specific incidence, relative (odds ratios) and population-attributable risks for defined exposures, and 28-day and 6-month case fatality ratios and other outcomes. CONCLUSIONS: Preliminary experience confirms the completeness of the surveillance methods, with no clear missed out-of-hospital cases of SAH with sudden death, and of high participation and reliable data collection procedures. CHERISH is well placed to provide reliable estimates of the burden of SAH in China.

pFind 2.0: a software package for peptide and protein identification via tandem mass spectrometry.

This paper describes the pFind 2.0 software package for peptide and protein identification via tandem mass spectrometry. Firstly, the most important feature of pFind 2.0 is that it offers a modularized and customized platform for third parties to test and compare their algorithms. The developers can create their own modules following the open application programming interface (API) standards and then add it into workflows in place of the default modules. In addition, to accommodate different requirements, the package provides four automated workflows adopting different algorithm modules, executing processes and result reports. Based on this design, pFind 2.0 provides an automated target-decoy database search strategy: The user can just specify a certain false positive rate (FPR) and start searching. Then the system will return the protein identification results automatically filtered by such an estimated FPR. Secondly, pFind 2.0 is also of high accuracy and high speed. Many pragmatic preprocessing, peptide-scoring, validation, and protein inference algorithms have been incorporated. To speed up the searching process, a toolbox for indexing protein databases is developed for high-throughput applications and all modules are implemented under a new architecture designed for large-scale parallel and distributed searching. An experiment on a public dataset shows that pFind 2.0 can identify more peptides than SEQUEST and Mascot at the 1% FPR. It is also demonstrated that this version of pFind 2.0 has better usability and higher speed than its previous versions. The software and more detailed supplementary information can both be accessed at http://pfind.ict.ac.cn/.