Identity search

Related to the identity search but unique to combinatorial libraries is a search to find the specific structures that are shared between two libraries. The result can be expressed, for each library, as a percentage overlap with the other library. This type of search could be useful in evaluating the development or purchase of a library, and in analyzing deconvolution experiments. As shown in Fig. 7, even simple combinatorial libraries can be challenging to compare. In this case, each library contains six explicit structures, and there are two in common, for a 33% overlap. 

Cooperative Searching for Timesaving. Many companies have made identical or almost identical searches, especially in broad fields, such as alkylation, oxidation, aviation fuels, and tranquilizers. This constitutes an unfortunate duplication of work. 

Ladies GS, Bannon GA, Silvanovich A, Cressman RF. Comparison of conventional FASTA identity searches with the 80 amino acid sliding window FASTA search for the elucidation of potential identities to known allergens. Mol Nutr Food Res. 2007 51(8) 985-998. 

Molecular formulas can be used as additional search criteria. Either complete formulas — similar to sum formula identity search — or partial formulas and atomic ranges can be specified, such as C5-8H8-1202. 

The workflow with WODCA starts with entering a target structure, the reaction product. The software automatically performs an identity search in the database to identify suitable starting materials. If no starting materials are found, the user can start a similarity search in the database. Similarity searches include 40 different criteria, such as the following ... 

The full GC/MS trace is analysed to locate the various components and candidate unknown spectra generated for searching in the reference databases using SIS-COM. The mass spectram database search system which comes with the MassLib package detailed below is called SISCOM (Search for Identical and Similar COM-ponents) [21]. The Identity search option looks for the unknown in the reference libraries and can handle binary mixtures as unknowns provided both substances are represented in the reference database. The identity search swaps to the similarity search mode if no identical hits have been found in the reference databases where characteristic ions in the unknown are searched in the reference libraries. 

Library searching techniques are of two kinds identity searches and similarity searches. Identity searches (i.e., searches requiring an exact match between the query and the reference) are successful only if the sought spectrum or structures are already in the reference library. If not, the search fails completely. In contrast, similarity searches depend on the metrics introduced into the representation of the spectra or structures. The metrics and consequently the distance or the similarity measure between the query object and the reference depend on the problem being studied hence, the results obtained on the basis of similarity are not directly comparable when the problems are from different fields. 

Library systems designed to retrieve references identical to the query are called identity search systems. Since the identity of any object (spectrum, chromatogram, chemical structure, set of chemical features) is well defined, the identity search is reduced to the binary decision identical/not identical. The system has to be insensitive to varying instrumental conditions, but there is no need to discriminate between different degrees of similarity. The identity search system is useful only in a limited range of applications for example, in the field of environmental control or drug control where the set of compounds that are expected or have to be identified are exactly specified. Any other, unspecified compound is irrelevant. In most other applications the unexpected compounds are of prime interest, so that the identity search is of limited use. 

An alternative, and highly efficient, structure search uses a hashing function, a computational procedure that takes some data record, such as a connection table or unique SMILES, and converts it to the computer address at which that record is stored." Although hashing functions may lead to more than one record with the same address, the detailed molecular comparisons need to be carried out for just those few molecules." " Because of canonicalization and hashing functions, identity searching is generally very fast. 

In the 1990s, Steven Stein from NIST took the former INCOS approach and extended it to the most common situations when unknown compounds are not present in the library. Structurally similar compounds can appear in the NIST library search hit list. The identity search presumes that the unknown compound is represented in the reference database, as it is designed to find the exact match to the unknown spectrum. The extended search mode for similarity should be used if it becomes apparent that the spectrum of the unknown compound is not present in the library. Stein also added probabilities to the hit list that give information about common substructures which may be present or absent in the unknown... 

In an identity search, a similarity metric that best discriminates between identity and nonidentity should be chosen, However, it should be noted that even if the compound whose structure is to be verified is present in the reference database, an exact match of spectral data may be unrealistic. There are intrinsic instrumental limitations, possible contaminants in the compound under study, differences in sampling techniques, limitations in the discriminatory power of the similarity metric used, and, possibly, unreliable reference data. Thus, the matching tolerance requirement for assigning structure must reflect these circumstances. Although no sharp boundary exists between an identity and a similarity search, in practice they are considered to be different and serve different purposes (see Section 3.2). 

If more than one spectrum consistent with the matching requirement for the identity search is retrieved (4), the structures corresponding to these spectra are retrieved (5). If the proposed structure is present in the set, the chemist, based on the structures of the retrieved compounds, must decide if verification has been achieved. 

The verification procedure can begin with an identity search for the proposed structure in the databases, followed by retrieval of the structure, if present, and comparison of its spectral properties with the observed spectral data. If a good fit is obtained, the chemist can conclude that the proposed structure is verified. However, it may be that there is another compound in the databases, possibly closely related in structure, the spectral properties of which match the observed spectral data as well or better. In this case, the identity structure search should... 

Addition of a nomenclature search progr uii, an identity search program and a search program based on the Edgewood CIDS structure keys (6), as well as some considerable refinement of the system... 

Figure 16. Example of IDENT search for a complete molecule...

The on-line system will perform 4 distinct types of searches 1) by accession number 2) by sample number 3) by full structure, or identity search 4) simple sub-structure search. 

Analysis of Research Proposals. The Army Medical Reseetrch and Development Command supports research in the directed synthesis of screening candidates. Twice yearly the Division of Eiqperi-mental Therapeutics reviews synthesis proposals. The proposed structures in each proposal are entered into the data base in the "XR" series and are also entered as identity searches to determine whether or not the compounds are already on hetnd cuid to identify duplication among the proposals. In addition, substructure searches for the major classes of compounds proposed are also run. Matches from both the identity eind sub-structure searches are then used to query the biology auid inventory files. The reviewer is presented with a report sequenced by proposal number providing him with all available information on the availability and activity of all specific compounds emd classes of compounds in each proposal. A similar procedure is used by contract monitors to review progress on synthesis contracts cind to prevent duplication of effort. 

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