Tandem mass spectral library search (MS/MS) is the fastest way to correctly annotate MS/MS spectra from screening small molecules in fields such as environmental analysis, drug screening, lipid analysis, and metabolomics. The confidence in MS/MS-based annotation of chemical structures is impacted by instrumental settings and requirements, data acquisition modes including data-dependent and data-independent methods, library scoring algorithms, as well as post-curation steps. We critically discuss parameters that influence search results, such as mass accuracy, precursor ion isolation width, intensity thresholds, centroiding algorithms, and acquisition speed. A range of publicly and commercially available MS/MS databases such as NIST, MassBank, MoNA, LipidBlast, Wiley MSforID, and METLIN are surveyed. In addition, software tools including NIST MS Search, MS-DIAL, Mass Frontier, SmileMS, Mass++, and XCMS to perform fast MS/MS search are discussed. MS/MS scoring algorithms and challenges during compound annotation are reviewed. Advanced methods such as the in silico generation of tandem mass spectra using quantum chemistry and machine learning methods are covered. Community efforts for curation and sharing of tandem mass spectra that will allow for faster distribution of scientific discoveries are discussed.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives.

We explore the mid-infrared (mid-IR) through ultraviolet (UV) spectral energy distributions (SEDs) of 119,652 luminous broad-lined quasars with 0.064 < z < 5.46 using mid-IR data from Spitzer and WISE, near-infrared data from Two Micron All Sky Survey and UKIDSS, optical data from Sloan Digital Sky Survey, and UV data from Galaxy Evolution Explorer. The mean SED requires a bolometric correction (relative to 2500Å) of BC 2500Å = 2.75 ± 0.40 using the integrated light from 1 µm-2 keV, and we further explore the range of bolometric corrections exhibited by individual objects. In addition, we investigate the dependence of the mean SED on various parameters, particularly the UV luminosity for quasars with 0.5 z 3 and the properties of the UV emission lines for quasars with z 1.6; the latter is a possible indicator of the strength of the accretion disk wind, which is expected to be SED dependent. Luminosity-dependent mean SEDs show that, relative to the highluminosity SED, low-luminosity SEDs exhibit a harder (bluer) far-UV spectral slope (α UV ), a redder optical continuum, and less hot dust. Mean SEDs constructed instead as a function of UV emission line properties reveal changes that are consistent with known Principal Component Analysis (PCA) trends. A potentially important contribution to the bolometric correction is the unseen extream-UV (EUV) continuum. Our work suggests that lower-luminosity quasars and/or quasars with disk-dominated broad emission lines may require an extra continuum component in the EUV that is not present (or much weaker) in high-luminosity quasars with strong accretion disk winds. As such, we consider four possible models and explore the resulting bolometric corrections. Understanding these various SED-dependent effects will be important for accurate determination of quasar accretion rates.