Mastering data pre-processing for accurate quantitative molecular profiling with liquid chromatography coupled to mass spectrometry

Identificatie van verstoringen in biologische systemen is de hoeksteen van biomedisch onderzoek. Het meten van veranderingen op het moleculaire niveau heeft het mogelijk gemaakt biomedisch onderzoek te begrijpen van belangrijke fysiologische en moleculaire mechanismen in levende systemen. Proteomics laat de analyse van deze systeemniveau moleculaire veranderingen en interacties toe in complexe biologische monsters. Gegevensafhankelijke acquisitie (DDA) is de meest gebruikte aanpak voor het uitgebreide profileren van eiwitten en metaboliet in bottom-up proteomics experimenten die zijn verkregen met behulp van LC-MS / MS. Dit proefschrift beschrijft nieuwe kwaliteitsbeoordelingsmethoden die gebruikt worden om orthogonaliteit te bestuderen in het retentietijddomein (scheidingsdimensie) en vitale pre-analytische factoren die de ionenintensiteit (uitleesdimensie) van LC-MS / MS datasets beïnvloeden. Dus volgende opmerkingen vormen de hoofddoelen van het proefschrift - - Samenvatting van diverse gegevensvoorbereidende stappen die betrokken zijn bij de behandeling van labelvrije LC-MS (/ MS) datasets, verkregen voor een typisch proteomics experiment. - Beschrijf het MS1-stadium van een LC-MS (/ MS) dataset als tweede-orde tensor (driedimensionale data). Bespreek verschillende fysio-chemische oorsprong en effecten van Orthogonaliteit in de twee scheidingsafmetingen (m / z en retentietijd) en uitlezing Dimensie (ionintensiteit). - Presentatie van een kwaliteitsbeoordelingsbenadering, die orthogonaliteit in de retentietijddimensie voor een paar LC-MS (/ MS) chromatogrammen evalueert na correctie Van monotone verschuivingen. - Propositie van een methode om ongeëvenaarde spectra te annoteren op basis van het begrip "identificatieoverdracht" na correctie van monotone verschuivingen tussen datasets en Beoordeel de FDR geassocieerd met bijpassende functies op basis van retentietijd en m / z-coördinaten tussen datasets. - Toepassing van Anova-Simultaneous Component Analysis (ASCA) om te bepalen welke pre-analytische factoren het ionintensiteitsdomein van LC-MS-eigenschappen beïnvloeden

Tutorial: Correction of shifts in single-stage LC-MS(/MS) data

Abstract Label-free LC-MS(/MS) provides accurate quantitative profiling of proteins and metabolites in complex biological samples such as cell lines, tissues and body fluids. A label-free experiment consists of several LC-MS(/MS) chromatograms that might be acquired over several days, across multiple laboratories using different instruments. Single-stage part (MS1 map) of the LC-MS(/MS) contains quantitative information on all compounds that can be detected by LC-MS(/MS) and is the data of choice used by quantitative LC-MS(/MS) data pre-processing workflows. Differences in experimental conditions and fluctuation of analytical parameters influence the overall quality of the MS1 maps and are factors hampering comparative statistical analyses and data interpretation. The quality of the obtained MS1 maps can be assessed based on changes in the two separation dimensions (retention time, mass-to-charge ratio) and the readout (ion intensity) of MS1 maps. In this tutorial we discuss two types of changes, monotonic and non-monotonic shifts, which may occur in the two separation dimensions and the readout of MS1 map. Monotonic shifts of MS1 maps can be corrected, while non-monotonic ones can only be assessed but not corrected, since correction would require precise modelling of the underlying physicochemical effects, which would require additional parameters and analysis. We discuss reasons for monotonic and non-monotonic shifts in the two separation dimensions and readout of MS1 maps, as well as algorithms that can be used to correct monotonic or to assess the extent non-monotonic shifts. Relation of non-monotonic shift with peak elution order inversion and orthogonality as defined in analytical chemistry is discussed. We aim this tutorial for data generator and evaluators scientists who aim to known the condition and approaches to produce and pre-processed comparable MS1 maps

Seamless Short Video Consumption Via a Web Browser or Application

The present disclosure describes computer-implemented systems and methods for assisting a user to navigate and consume videos hosted on third-party platforms. In response to a user query, a plurality of video results responsive to the user query are displayed and upon selection of one of the plurality of video results, a web browser retrieves and renders a webpage including the video from the respective video hosting platform. The system can playback the video and generate similar video results from a plurality of video hosting platforms pertaining to a given user query

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A gravitational-wave standard siren measurement of the Hubble constant

On 17 August 2017, the Advanced LIGO 1 and Virgo 2 detectors observed the gravitational-wave event GW170817-a strong signal from the merger of a binary neutron-star system 3 . Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO-Virgo-derived location of the gravitational-wave source 4-6 . This sky region was subsequently observed by optical astronomy facilities 7 , resulting in the identification 8-13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first 'multi-messenger' astronomical observation. Such observations enable GW170817 to be used as a 'standard siren' 14-18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic 'distance ladder' 19 : the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements 20,21 , while being completely independent of them. Additional standard siren measurements from future gravitationalwave sources will enable the Hubble constant to be constrained to high precision