Networking Mass Spectrometer Data Systems for Improved Productivity and Electronic Archiving of Data

Several Finngan-MAT mass spectrometer data systems were networked together to achieve the following two primary objectives: (1) to allow access to mass spectrometry data and data processing functions from remote locations without affecting simultaneous data acquisition at the instruments, and (2) to electronically archive mass spectrometry data at a central location on a high-capacity, fast-access device that allows rapid retrieval of archived data for all data processing operations at all locations. UNIX workstations, IBM PC/AT-compatible computers, and Data General Nova minicomputers were connected via Ethernet interfaces to allow rapid data transfer among all systems as well as X-Windows access to UNIX-based systems. Bridging techniques were used to isolate possible high-traffic areas of the network and to enable security measures for adequate protection of files. Additionally, serial connections were made through a Northern Telecom phone system to provide remote terminal access to the Data General Nova-based systems. Use of these connectivity techniques significantly improved productivity by allowing retrieval, processing, and printing of data from remote locations, such as office areas, without affecting data acquisition, processing, and printing performed simultaneously at the instruments. For archival purposes, data files are electronically stored on high-capacity magneto-optical disks for rapid retrieval. A highcapacity fixed disk is also available for centralized temporary data file storage. A Digital Equipment Corporation DECstation 2100 UNIX workstation was used as the file server for centralized data storage while being simultaneously utilized as the data system computer for one of the mass spectrometers. Utilization of this UNIX-based file server system in conjunction with Ethernet connectivity techniques provides a centralized, rapid-access, high-capacity, cost- and space-efficient method for electronic archival of mass spectrometry raw data recorded at all of the instruments.     

A review of the CLIP system for the quantitative analysis of two-dimensional electrophoresis gels

This paper reviews the CLIP image processing system for the complete analysis of two-dimensional electrophoresis images. The analysis problem for two-dimensional gel images can be broken down into three issues: segmentation of individual gel images, alignment and comparison of pairs of gel images, and information storage and retrieval. This paper describes these problems and reviews how the CLIP system handles each of them. Segmentation is the location and isolation of each protein spot on an individual gel image and also the extraction of individual spot data such as position, area and volume. There are three basic stages: background field correction, noise filtering, spot detection and information extraction. Alignment and comparison of gel images involves matching protein spots between two gels. This can be quite difficult because there is not a simple relationship which can transform one gel image onto another. The database issues concern storing all the information which has been obtained from the above operations such that retrieval of this information can be readily performed. The advantage of the CLIP system over others is speed of processing. CLIP series computers use one processor for every pixel of the camera image such that image processing algorithms run in parallel. The main disadvantage is in the cost of these machines. With the declining trend in the cost of parallel processors, these machines will become more and more viable alternatives. This papers reviews the algorithms for the analysis of two-dimensional gels. It is shown that CLIP is flexible enough to perform more than one type of algorithm for a particular operation.     

Evaluation of the suitability of archival Bouin-fixed paraffin-embedded tissue specimens to proteomic investigation

Bouin's solution has been used for over a century as a common fixative in several pathology laboratories worldwide. Therefore, a considerable number of Bouin-fixed paraffin-embedded (BFPE) tumor samples of various origin are available in hospital repositories as a powerful information mine for clinical investigations. To date, however, such archived tissues have not been subjected to a systematic study aimed to evaluate their potential use in proteomics. In this report, we investigated whether archival BFPE tissue specimens could be exploited for proteomic studies, upon application of protein extraction and proteomic analysis methods previously optimized for formalin-fixed samples. As a result, gastric BFPE protein extracts exhibited poor suitability for 2D-PAGE analysis, whereas over 300 unique proteins could be successfully detected when extracts were subjected to SDS-PAGE followed by LC-MS/MS (GeLC-MS/MS). Among these, several known markers for gastric cancer and normal gastric functionality were identified, indicative of biological and clinical significance of proteomic data mined from BFPE tissues. A quantitative and qualitative comparison of FFPE and BFPE tissue proteomes was also performed, and results are reported. In conclusion, we demonstrated that BFPE specimens can be analyzed by means of a proteomic approach such as GeLC-MS/MS. Although considerable molecular biases and technical constraints exist, BFPE tissue archives can be fruitfully exploited for gathering proteomic data from particularly precious samples.     

Object oriented database and electronic notebook for transmission electron microscopy.

As high-resolution biological transmission electron microscopy (TEM) has increased in popularity over recent years, the volume of data and number of projects underway has risen dramatically. A robust tool for effective data management is essential to efficiently process large data sets and extract maximum information from the available data. We present the Electron Microscopy Electronic Notebook (EMEN), a portable, object-oriented, web-based tool for TEM data archival and project management. EMEN has several unique features. First, the database is logically organized and annotated so multiple collaborators at different geographical locations can easily access and interpret the data without assistance. Second, the database was designed to provide flexibility to the user, so it can be used much as a lab notebook would be, while maintaining a structure suitable for data mining and direct interaction with data-processing software. Finally, as an object-oriented database, the database structure is dynamic and can be easily extended to incorporate information not defined in the original database specification.     

Analysis of commercial and public bioactivity databases

Activity data for small molecules are invaluable in chemoinformatics. Various bioactivity databases exist containing detailed information of target proteins and quantitative binding data for small molecules extracted from journals and patents. In the current work, we have merged several public and commercial bioactivity databases into one bioactivity metabase. The molecular presentation, target information, and activity data of the vendor databases were standardized. The main motivation of the work was to create a single relational database which allows fast and simple data retrieval by in-house scientists. Second, we wanted to know the amount of overlap between databases by commercial and public vendors to see whether the former contain data complementing the latter. Third, we quantified the degree of inconsistency between data sources by comparing data points derived from the same scientific article cited by more than one vendor. We found that each data source contains unique data which is due to different scientific articles cited by the vendors. When comparing data derived from the same article we found that inconsistencies between the vendors are common. In conclusion, using databases of different vendors is still useful since the data overlap is not complete. It should be noted that this can be partially explained by the inconsistencies and errors in the source data.     

C library for topological study of the electronic charge density

The topological study of the electronic charge density is useful to obtain information about the kinds of bonds (ionic or covalent) and the atom charges on a molecule or crystal. For this study, it is necessary to calculate, at every space point, the electronic density and its electronic density derivatives values up to second order. In this work, a grid‐based method for these calculations is described. The library, implemented for three dimensions, is based on a multidimensional Lagrange interpolation in a regular grid; by differentiating the resulting polynomial, the gradient vector, the Hessian matrix and the Laplacian formulas were obtained for every space point. More complex functions such as the Newton–Raphson method (to find the critical points, where the gradient is null) and the Cash–Karp Runge–Kutta method (used to make the gradient paths) were programmed. As in some crystals, the unit cell has angles different from 90°, the described library includes linear transformations to correct the gradient and Hessian when the grid is distorted (inclined). Functions were also developed to handle grid containing files (grd from DMol® program, CUBE from Gaussian® program and CHGCAR from VASP® program). Each one of these files contains the data for a molecular or crystal electronic property (such as charge density, spin density, electrostatic potential, and others) in a three‐dimensional (3D) grid. The library can be adapted to make the topological study in any regular 3D grid by modifying the code of these functions. © 2012 Wiley Periodicals, Inc.     

An unusual systematic behaviour of detection limits for elements from 55Cs to 73Ta

A representative database for detection limits for all elements from ⁵⁵Cs to ⁷³Ta reveals that these limits are governed by a systematic zigzag pattern, according to which the odd atomic number elements have systematically lower detection limits than the even atomic number neighbour elements. This is true even when the actual detection limits vary by several orders of magnitude. We propose that such a systematic pattern be used as a requisite analytical criterion to evaluate the detection limit data, and any departure from this pattern be looked on with caution to check the analytical technique for any interference or matrix effect problems.Electronic Supplementary Material Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.     

VSDMIP: virtual screening data management on an integrated platform

A novel software (VSDMIP) for the virtual screening (VS) of chemical libraries integrated within a MySQL relational database is presented. Two main features make VSDMIP clearly distinguishable from other existing computational tools: (i) its database, which stores not only ligand information but also the results from every step in the VS process, and (ii) its modular and pluggable architecture, which allows customization of the VS stages (such as the programs used for conformer generation or docking), through the definition of a detailed workflow employing user-configurable XML files. VSDMIP, therefore, facilitates the storage and retrieval of VS results, easily adapts to the specific requirements of each method and tool used in the experiments, and allows the comparison of different VS methodologies. To validate the usefulness of VSDMIP as an automated tool for carrying out VS several experiments were run on six protein targets (acetylcholinesterase, cyclin-dependent kinase 2, coagulation factor Xa, estrogen receptor alpha, p38 MAP kinase, and neuraminidase) using nine binary (actives/inactive) test sets. The performance of several VS configurations was evaluated by means of enrichment factors and receiver operating characteristic plots. ángel R. Ortiz deceased on May 5, 2008.     

Multiplex PCR with minisequencing as an effective high-throughput SNP typing method for formalin-fixed tissue

Extensive collections of formalin-fixed paraffin-embedded (FFPE) tissues exist that could be exploited for genetic analyses in order to provide important insights into the genetic basis of disease or host/pathogen cointeractions. We report here an evaluation of a 44 SNP multiplex genotyping method, multiplex PCR with minisequencing (MPMS), on 92 DNA extractions performed on six archival FFPE samples of variable DNA quality, which date between 9 and 25 years old. On the three extracts with highest quality, we found the assay efficiency to be near 100%. However, the efficiency of the lowest quality extracts varied significantly. In this study, we demonstrate that although direct measures of DNA concentration in the extracts provide no useful information with regard to subsequent MPMS success, the success of the assay can be determined to some degree a priori, through initial screening of the DNA quality using a simple quantitative real-time PCR (qPCR) assay for nuclear DNA, and/or an assay of the maximum PCR amplifiable size of nuclear DNA. MPMS promises to be of significant use in future genetic studies on FFPE material. It provides a streamlined approach for retrieving a large amount of genetic information using simple, single reactions and minute amounts of archival tissue/DNA. In the light of this evidence, we suggest that the systematic screening of FFPE collections may in the future provide valuable insights into the past.     

Mathematical correction for fingerprint similarity measures to improve chemical retrieval

In many modern chemoinformatics systems, molecules are represented by long binary fingerprint vectors recording the presence or absence of particular features or substructures, such as labeled paths or trees, in the molecular graphs. These long fingerprints are often compressed to much shorter fingerprints using a simple modulo operation. As the length of the fingerprints decreases, their typical density and overlap tend to increase, and so does any similarity measure based on overlap, such as the widely used Tanimoto similarity. Here we show that this correlation between shorter fingerprints and higher similarity can be thought of as a systematic error introduced by the fingerprint folding algorithm and that this systematic error can be corrected mathematically. More precisely, given two molecules and their compressed fingerprints of a given length, we show how a better estimate of their uncompressed overlap, hence of their similarity, can be derived to correct for this bias. We show how the correction can be implemented not only for the Tanimoto measure but also for all other commonly used measures. Experiments on various data sets and fingerprint sizes demonstrate how, with a negligible computational overhead, the correction noticeably improves the sensitivity and specificity of chemical retrieval.     

cclib: a library for package-independent computational chemistry algorithms

There are now a wide variety of packages for electronic structure calculations, each of which differs in the algorithms implemented and the output format. Many computational chemistry algorithms are only available to users of a particular package despite being generally applicable to the results of calculations by any package. Here we present cclib, a platform for the development of package-independent computational chemistry algorithms. Files from several versions of multiple electronic structure packages are automatically detected, parsed, and the extracted information converted to a standard internal representation. A number of population analysis algorithms have been implemented as a proof of principle. In addition, cclib is currently used as an input filter for two GUI applications that analyze output files: PyMOlyze and GaussSum.     

ProteinQuant Suite: a bundle of automated software tools for label-free quantitative proteomics

In simplifying the evaluation and quantification of high-throughput label-free quantitative proteomic data, we introduce ProteinQuant Suite. It comprises three standalone complementary computer utilities, namely ProtParser, ProteinQuant, and Turbo RAW2MGF. ProtParser is a filtering utility designed to evaluate database search results. Filtering is performed according to different criteria that are defined by the end-user. ProteinQuant then utilizes this parsed list of peptides and proteins in conjunction with mzXML or mzData files generated from the raw files for quantification. This quantification is based on the automatic detection and integration of chromatographic peaks representative of the liquid chromatography/mass spectrometry (LC/MS) elution profiles of identified peptides. Turbo RAW2MGF was developed to extend the applicability of ProteinQuant Suite to data collected from different types of mass spectrometers. It directly processes raw data files generated by Xcalibur, a ThermoElectron data acquisition software, and generates a MASCOT generic file (MGF). This file format is needed since the protein identification results generated by the database search employing this file format include information required for the precise identification and quantification of chromatographic peaks. The performance of ProteinQuant Suite was initially validated using LC/MS/MS generated for a mixture of standard proteins as well as standard proteins spiked in a complex biological matrix such as blood serum. Automated quantification of the collected data resulted in calibration curves with R(2) values higher than 0.95 with linearity spanning over more than 2 orders of magnitude with peak quantification reproducibility better than 15% (RSD). ProteinQuant Suite was also applied to confirm the binding preference of standard glycoproteins to Con A lectin using a sample consisting of both standard glycoproteins and proteins.     

Information system, data bases, and on-line services of the Japan Information Center of Science and Technology (JICST)

The JICST information processing system consists of the data-base production system, authority file management system, bibliographic retrieval system, and printed issue compiling system. The bibliographic retrieval service based on the JICST On-line Information System (JOIS-I) has been available through leased line since 1976 and now also through dial-up line, which covers five data bases: the JICST bibliographic and on-going research information files, CA Condensates, MEDLARS, and TOXLINE files. The on-line output in Japanese kanji is also available. The newly revised JOIS-II system is now being developed.     

GammaLab: a suite of programs for k0-NAA and gamma-ray spectrum analysis

The GammaLab is a collection of computer codes, written in MATLAB, for performing calculations involved in k ₀ neutron activation analysis. The main features of the program include calibrations including energy-channel, energy-FWHM and energy-efficiency for different geometries, background subtraction, nuclide identification, spectral interference correction, elemental concentration and limit of detection determination. The data input is taken from two files one is the spectrum file stored in IAEA ASCII format and other is report file containing peak energy and peak area data. The information about sample, irradiation and counting conditions, background spectra are retrieved from QAQCData database. GammaLab takes nuclear data such as gamma lines, emission probabilities, half-lives, and k ₀ factors from NucData database. The sample results which contain elemental concentrations with uncertainties are stored in the QAQCData database. The program has been evaluated by analyzing several hundred spectra and results were found satisfactory.     

Electron impact total cross section for acetylene over an extensive range of impact energies (1 eV-5000 eV)

Comprehensive study on electron impact for acetylene molecule is performed in terms of eigenphase diagram, electronic excitation cross sections as well as total cross section calculations from 1 eV to 5000 eV in this article. Computation of cross section over such a wide range of energy is reported for the first time. We have employed two distinct formalisms to derive cross sections in these impact energies. From 1 eV to ionization threshold of the target we have used the ab initio R-matrix method and then spherical complex optical potential method beyond that. At the crossing point of energy, both theories matched quite well and hence prove that they are consistent with each other. The results presented here expectedly give excellent agreement with other experimental values and theories available. The techniques employed here are well established and can be used to predict cross sections for other targets where data are scarce or not available. Also, this methodology may be integrated to online database such as Virtual Atomic and Molecular Data Centre to provide cross section data required by any user.     

Learning from the data: mining of large high-throughput screening databases

High-throughput screening (HTS) campaigns in pharmaceutical companies have accumulated a large amount of data for several million compounds over a couple of hundred assays. Despite the general awareness that rich information is hidden inside the vast amount of data, little has been reported for a systematic data mining method that can reliably extract relevant knowledge of interest for chemists and biologists. We developed a data mining approach based on an algorithm called ontology-based pattern identification (OPI) and applied it to our in-house HTS database. We identified nearly 1500 scaffold families with statistically significant structure-HTS activity profile relationships. Among them, dozens of scaffolds were characterized as leading to artifactual results stemming from the screening technology employed, such as assay format and/or readout. Four types of compound scaffolds can be characterized based on this data mining effort: tumor cytotoxic, general toxic, potential reporter gene assay artifact, and target family specific. The OPI-based data mining approach can reliably identify compounds that are not only structurally similar but also share statistically significant biological activity profiles. Statistical tests such as Kruskal-Wallis test and analysis of variance (ANOVA) can then be applied to the discovered scaffolds for effective assignment of relevant biological information. The scaffolds identified by our HTS data mining efforts are an invaluable resource for designing SAR-robust diversity libraries, generating in silico biological annotations of compounds on a scaffold basis, and providing novel target family specific scaffolds for focused compound library design.     

Construction of a data base for cobalt-59 nuclear magnetic resonance spectrometry

The TOOL-IR. PDB and COOD systems are compared for the construction of data bases for ⁵⁹Co-n.m.r. bibliographic and spectral data. The spectral data used are the chemical shifts from several different standards, and the line widths and coupling constants (if present). The PDB system is effective for storage and retrieval of bibliographic data, but the COOD system is better for the retrieval of spectral data, and for combination of data files on literature and chemical shifts.     

Array files for computational chemistry: MP2 energies

A simple message‐passing implementation for distributed disk storage, called array files (AF), is described. It is designed primarily for parallelizing computational chemistry applications but it should be useful for any application that handles large amounts of data stored on disk. AF allows transparent distributed storage and access of large data files. An AF consists of a set of logically related records, i.e., blocks of data. It is assumed that the records have the typical dimension of matrices in quantum chemical calculations, i.e., they range from 0.1 to ～32 MB in size. The individual records are not striped over nodes; each record is stored on a single node. As a simple application, second‐order Møller‐Plesset (MP2) energies have been implemented using AF. The AF implementation approaches the efficiency of the hand‐coded program. MP2 is relatively simple to parallelize but for more complex applications, such as Coupled Cluster energies, the AF system greatly simplifies the programming effort. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007.     

mHDFS-HoF: A generalized multilevel homodesmotic fragment-separation reaction based program for heat-of-formation calculation for acyclic hydrocarbons

Based on our modified classification of elemental species, a framework for automatic generation of multilevel Homodesmotic fragment-separation (mHDFS) reactions for chemical species was proposed. Combined the mHDFS framework with a database of heat of formation (HoF) and the calculated electronic structure data for the elemental mHD species, the mHDFS-HoF program was constructed in C/C++ language to calculate heat of formation for a species of interest on-the-fly. Using the electronic structure data calculated at CBS-QB3 level of theory for the elemental mHD species, applications and robustness of the code were discussed with several acyclic hydrocarbon systems including neutral and radical species. On-going work and extension to other systems were also discussed. The program and the supporting files can be freely downloaded at https://sites.google.com/view/mhdfs/ . © 2019 Wiley Periodicals, Inc.