A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments

<p>Abstract</p> <p>Background</p> <p>Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies.</p> <p>Results</p> <p>A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant <it>Leishmania mexicana </it>parasites.</p> <p>Conclusion</p> <p>We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.</p

Compensation of victims in the context of peace operations of international organizations

This thesis deals with the protection of children in international refugee law. The status of a person seeking international protection under international law is primarily regulated by the Convention Relating to the Status of Refugees. However, this Convention does not expressly address the specific situation of the child asylum seeker. By adopting a binding Convention on the Rights of the Child (CRC), the broad catalogue of basic civil, political, economic, social and cultural rights of children has been confirmed. It includes the right of a child seeking international protection to obtain the necessary protection and humanitarian assistance when the child wants to exercise its rights under the CRC or other conventions of international law of human rights. CRC includes, inter alia, four fundamental principles, the elimination of discrimination, the right to life, survival and development, respect for the child's position and the principle of the best interests of the child. The goal of this thesis is to determine whether and how the position of the child seeking international protection under the international refugee law has been influenced by the CRC and by the principle of the best interests of the child. The thesis is divided into four chapters, the first two chapters deal with the historical..

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments-3

<p><b>Copyright information:</b></p><p>Taken from "A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments"</p><p>http://www.biomedcentral.com/1471-2105/8/419</p><p>BMC Bioinformatics 2007;8():419-419.</p><p>Published online 29 Oct 2007</p><p>PMCID:PMC2194738.</p><p></p>ments of polar extracts were processed, generating eight peak lists. The peak lists were aligned with the dynamic programming for a range of the gap penalty parameter between 0.10 and 0.55 (the retention time tolerance was fixed D = 2.5 s), and the resulting alignment tables were compared to the correct alignment table built manually. The top panel shows the total number of errors in the alignment. The middle panel shows the number of errors of type A (solid line) and type B (dashed line). The bottom panel shows the total number of metabolites in the resulting alignment. The correct number of metabolites is 173, shown in the dashed line

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments-1

<p><b>Copyright information:</b></p><p>Taken from "A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments"</p><p>http://www.biomedcentral.com/1471-2105/8/419</p><p>BMC Bioinformatics 2007;8():419-419.</p><p>Published online 29 Oct 2007</p><p>PMCID:PMC2194738.</p><p></p>shown with peak similarity (color coding is according to the scale between 0 and 1). For each score matrix the two axis refer to two peak lists to be aligned, with 14 signal peaks in each list (stationary phase peaks plotted along the x-axis and mid-log phase peaks plotted on the y-axis). The top panel shows the score matrix based on the retention time similarities only (as given the second term in the Equation [2]). The middle panel shows the score matrix based on the similarities in mass spectra taken at the peak apex (as given by the first term in the Equation [2]). The bottom panel is the total peak similarity function, as given by the Equation [2] (this is element-by-element product of the retention time and mass spectra score matrices). The traceback resulting from the application of dynamic programming is also shown in bottom panel. From the traceback the best alignment of peaks was deduced, as shown in Figure 3(b)

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments-0

<p><b>Copyright information:</b></p><p>Taken from "A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments"</p><p>http://www.biomedcentral.com/1471-2105/8/419</p><p>BMC Bioinformatics 2007;8():419-419.</p><p>Published online 29 Oct 2007</p><p>PMCID:PMC2194738.</p><p></p>each segment. Panel b. The peak matching after dynamic programming peak alignment (see also Figure 4)

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London