Forward library search

Two types of library search have been developed. The first type, called forward search, compares the new spectrum with the spectra stored in the library and looks for the best match of the spectra. The second type, called reverse search, checks for the possible presence in the new spectra of a spectrum chosen in the library. 

Kwiatkowski, J. Riepe, W. A Combined Forward-Reverse Library Search System for the Identification of Low-Resolution Mass Spectra. Anal. Chim. Acta 1979, 772,219-231. 

Library search is usually performed in the "forward" mode, i.e., by comparing the coded spectrum of interest to every single spectrum within the library. The method of "reverse" search, i.e. comparing each library to the unknown, is slower but allows the detection of small components (poorly resolved) in mixtures (14). 

Display and selection Plotting of TIC, MS, MC, SIM Library search Forward ... 

Finally in this table, the library search is divided into two kinds The so called forward variant which has been mostly used and the reverse one which seems a most interesting development. The latter has recently been discussed in papers by McLafferty t ad. (48) and by Abramson (34), and was recently used by Green l. (8), apparently with great success. 

A mode of the PBM search procedure, which only uses the forward search capability of the library search, -> also Forward Hbrary search. 

The large peak at scan 502 (Fig. 1.7) does not interfere with the ability of the software to quantify the sample. Although the compound eluting at scan 502 was not one of the target compounds in the library being reverse-searched, it was possible to identify it by forward-searching the NBS library present on the system. The greatest similarity was in the comparison of the unknown with the spectrum of benzaldehyde. 

In the forward search, all of die ions in both the library spectrum and the unknown specdiun are used in the calculation of the fit factor, while in the reverse search only the ions in the library specdiun are used in this calculation. Forward searches work well only for pure compounds, while die reverse search is admirably suited for dealing widi die composite spectra fiom mixtures. 

In addition to conventional sequence motifs (Prosite, BLOCKS, PRINTS, etc.), the compilation of structural motifs indicative of specific functions from known structures has been proposed [268]. This should improve even the results obtained with multiple (one-dimensional sequence) patterns exploited in the BLOCKS and PRINTS databases. Recently, the use of models to define approximate structural motifs (sometimes called fuzzy functional forms, FFFs [269]) has been put forward to construct a library of such motifs enhancing the range of applicability of motif searches at the price of reduced sensitivity and specificity. Such approaches are supported by the fact that, often, active sites of proteins necessary for specific functions are much more conserved than the overall protein structure (e.g. bacterial and eukaryotic serine proteases), such that an inexact model could have a partly accurately conserved part responsible for function. As the structural genomics projects produce a more and more comprehensive picture of the structure space with representatives for all major protein folds and with the improved homology search methods linking the related sequences and structures to such representatives, comprehensive libraries of highly discriminative structural motifs are envisionable. 

Combinatorial chemistry has provided the means to synthesize literally billions of molecules, a major step forward in the exploration of molecular space. This random or brute-force approach to the search for new leads has been a major disappointment in its contribution to product pipelines (186) and the sacrifice of quality for quantity (187). However, combinatorial exploration around lead compounds or pharmacophores to generate dedicated libraries, when coupled with high-throughput screening, clearly provides an economical and efficient way to rapidly generate lead compounds (188). 

When peaks are incompletely separated identification may still be possible using a reverse search. The ability of an algorithm to match two or more components in the mass spectrum of a mixture is aided by requiring only that the peaks of the reference spectrum are present in the unknown spectrum rather than the other way round, as for a normal (or forward) search. The hit list of retrieved library spectra should then represent the compounds in the spectrum of the mixture provided that their spectra are present in the reference library. Subtracting the best-hit library spectrum from the mixture spectrum produces a residual spectrum that can then be matched against the other spectra in the hit list in a forward search. In a sequential process identification of the component spectra may be achieved. 

The forward search is the most rapid but demands unknown spectra of pure compounds to produce good results. If however the unknown spectrum includes peaks from unwanted impurities or of a mixture then it will not work correctly. The alternative reverse search strategy although slower is now required, whereby the resulting hit hst shows the best reference spectrum in the library as found in the unknown data. Peaks in the unknown which do not appear in the Hbrary... 

There are attractive features in the reverse search which, as I can understand it, ought to be utilized as the primary computerized search in situations such as toxicological MS, where a library limited to 100 compounds often will suffice. In cases where this primary search does not result a forward search is still possible, "manually or by computer. In the latter case the... 

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