Publications: Peer-Reviewed

In its June 30, 2009 edition, Rapid Communications in Mass Spectrometry published Correlogic’s study, “A Method for Assessing and Maintaining the Reproducibility of Mass Spectrometric Analyses of Complex Samples.” The study identifies a strategy for detecting and compensating for time-dependent drift in the ion source of an electrospray mass spectrometer when applied to the analysis of human serum samples. It is part of Correlogic’s ongoing development of new methods to improve the reproducibility of LC/MS platforms for the discovery of biomarkers.

In its February 2009 issue, the peer-reviewed journal PLoS ONE published Correlogic’s study “Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer”. This study represents part of Correlogic’s development of a serum-based multivariate assay to distinguish women with ovarian cancer from those with benign conditions. The research utilized 176 case and 187 control samples from patients presenting for surgery at multiple sites throughout the United States. From a panel of 104 antigens, 44 autoimmune and 56 infectious disease markers, Correlogic scientists identified an 11-analyte profile that appeared informative for all stages and common subtypes of ovarian cancer. Using a testing set of 245 samples, approximately twice the size of the model building set, scientists achieved 91.3% sensitivity and 88.5% specificity.

In its November 2008 edition, the Journal of the American Society for Mass Spectrometry published Correlogic’s “A Method for Monitoring and Controlling Reproducibility of Intensity Data in Complex Electrospray Mass Spectra: A Thermometer Ion-based Strategy”. This paper builds on the work Correlogic presented at the ASMS annual meeting June 3, 2008 and refines and implements components of Correlogic’s patent-pending strategy for monitoring and optimizing the performance of mass spectrometers for use in pattern analysis. This work details the use of mixtures of thermometer ions to sensitively probe and monitor the factors in an electrospray ionization source that impact the intensity axis of complex spectral data. The study proposes how the approach can be used to correct for time-dependent spectral-drift on a single instrument and intrinsic differences in spectral content between instruments. The study also presents a strategy for automating the process.

In its October 2008 issue, the American Association for Cancer Research’s peer-reviewed journal, Cancer Epidemiology, Biomarkers and Prevention, published “Multianalyte profiling of serum antigens and autoimmune and infectious disease molecules to identify biomarkers dysregulated in epithelial ovarian cancer”. In collaboration with Rules-Based Medicine (RBM), a multiplex assay developer and manufacturer based in Austin, TX, Correlogic scientists assessed the dysregulation of more than 200 serum molecules in ovarian cancer. Using RBM’s rigorously qualified, high-throughput, multiplexed immunoassays we assayed the panel of molecules and evaluated them for independent ovarian cancer diagnostic potential. The study examined 294 ovarian cancer and benign samples, identifying 77 biomarkers that were dysregulated in the ovarian cancer samples. Cancer antigen 125 (CA-125), C-reactive protein, epidermal growth factor receptor, interleukin 10, interleukin 8, connective tissue growth factor, haptoglobin, and tissue inhibitor of metalloproteinase 1 stood out as most discriminatory. These findings point to the absence of a single diagnostic marker and support the expanding interest in the use of multivariate assays, which form the ongoing focus of Correlogic’s work.

The August 2008 issue of the American Association for Cancer Research’s peer-reviewed journal, Cancer Epidemiology, Biomarkers and Prevention, published “Assessment of Serum Proteomics to Detect Large Colon Adenomas”. Scientists from Correlogic and the Departments of Medicine, Epidemiology, and Biostatistics, University of North Carolina at Chapel Hill employed Correlogic’s Proteome Quest^® technology to identify patients with large colorectal adenomas. The preponderance of colorectal cancers are thought to arise from large adenomatous colon polyps. These pre-cancerous polyps are a critical target for cancer screening. After removal of inappropriate samples, we were able to distinguish patients with large adenomas from those with normal colons, suggesting that a larger, more controlled study will show further enhanced results.

The June 2006 issue of the peer-reviewed journal, Biomolecular Engineering, published “Novel technology for rapid species-specific detection of Bacillus spores”. Correlogic’s Dr. Brian Mansfield, Dr. Ping Yip and Dr. Ben Hitt, and colleagues from the Charles Stark Draper Laboratory and Tufts University School of Medicine are authors of this paper.  Using pyrolysis-micromachined differential mobility spectrometry (DMS) and Correlogic’s genetic algorithms to provide a fingerprint that identifies each species, researchers were able to distinguish among bacillus species closely related to Bacillus anthracis (the causative agent in anthrax).  Results showed over 90 percent accuracy with a sensitivity of detection of 5,000 spores, significantly below the median infectious dose of 8,000 to 10,000 spores and well below the median lethal dose of ~62,000 spores.  Few existing rapid detection techniques detect below 100,000 spores.

The powerful combination of the DMS machine and Correlogic’s technology shows promise for portable, near-real-time accurate detection of spores.  In a more generalized setting, it may also be possible to detect and identify other harmful bacteria such as the Clostridia, which cause tetanus, diarrhea, botulism and food poisoning. 

The June 2006 edition of Experimental Hematology published our research, “Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis,” in which Correlogic’s technology was applied to detection of acute graft versus host disease (GVHD).

Rapid rejection of transplanted tissue is a life-threatening complication tissue transplantation, and timely detection is difficult because current tissue-based tests are time-consuming and invasive. In this study scientists used Correlogic’s technology to accurately distinguish GVHD samples from both post-transplant non-GVHD samples and pre-transplant samples (100 percent specificity and 100 percent sensitivity in both cases). We were also able to distinguish pre-transplant from post-transplant non-GVHD samples (100 percent specificity and 94 percent sensitivity). These results suggest a potential application of our technology as a rapid and accurate method to diagnose acute GVHD.

Note: This study presents data generated several years ago. Correlogic’s technology platform is now based on high-resolution, orthogonal time-of-flight mass spectrometry. This research was conducted under a CRADA with the FDA and NCI, which concluded in 2004. Correlogic has had no further relationship with the FDA/NCI scientists involved (See Congressional hearings 2004).

The September 15, 2005 issue of the peer-reviewed journal Analytical Chemistry publishes “Species-Specific Bacteria Identification Using Differential Mobility Spectrometry and Bioinformatics Pattern Recognition”.  Brian Mansfield, Correlogic’s VP for Research and Development, is one of the two co-first authors, and Correlogic’s Ben Hitt and Ping Yip are also co-authors of the paper. The collaboration involved Charles Stark Draper Labs, Massachusetts General Hospital and others. Scientists used a portable, micromachined differential mobility spectrometer in conjunction with Correlogic’s “Hidden Patterns” and Proteome Quest technology, to identify and differentiate between live bacteria based on analysis of the gases given off by the growing bacterial cultures.  The results have implications for diagnosis of bacterial infections using breath analysis. Other applications may include detection and identification of microbial growth in building materials and veterinary uses.

In June 2005, the peer-reviewed journal Endocrine-Related Cancer, publishes “Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma,” a paper co-authored by Correlogic’s Chief Science Officer Ben Hitt, researchers at the NCI/FDA, the Institute of Child Health and Human Development, and others.  This research, based on the use of Correlogic’s pattern recognition approach and technology, demonstrated the applicability of pattern discovery and recognition to differential diagnosis of malignant and benign disease. Researchers identified combinations of low molecular weight molecules that could distinguish 100 percent of metastatic pheochromocytomas from benign cases in a blinded validation set.  Metastatic lesions occur in up to 36 percent of patients with pheochromocytoma.  Currently there is no reliable way to detect or predict which patients are at risk for metastatic pheochromocytoma.

The journal, Arthritis and Rheumatism publishes in the March 2005 issue the results of our research, “A Serum Proteomic Approach To Gauging The State Of Remission In Wegener’s Granulomatosis”, using Correlogic’s hidden patterns approach and pattern recognition and discovery technology to distinguish active disease from remission in Wegener’s disease patients. This marks the first publication of the application of Correlogic’s approach and technology to detection of non-cancer diseases. The study was performed by Correlogic scientists, scientists from the Johns Hopkins University School of Medicine, the Mayo Clinic, Cleveland Clinic, Boston University School of Medicine, Beth Israel Medical Center, Duke University, University of California at SF, University of Michigan Medical School, and NCI/FDA. By precisely identifying when stable remission is achieved, this approach could help physicians calibrate the use of potentially toxic drug therapy.

The October 2004 issue of The Journal of Urology publishes “Serum Proteomic Profiling Can Discriminate Prostate Cancer From Benign Prostates In Men With Total Prostate Specific Antigen Levels Between 2.5 and 15.0 NG/ML.” This paper, co-authored by researchers at FDA/NCI; Correlogic’s, Ben Hitt and Wes Wiggins; and others, presents our research on prostate cancer. Applying Correlogic’s technology to the serum of men with elevated PSA, the research successfully discriminated between men with benign processes and men with prostate cancer. This included men with PSA within the diagnostic gray zone.

On June 2, 2004, the peer-reviewed journal Endocrine-Related Cancer, published “High-Resolution Serum Proteomic Features for Ovarian Cancer Detection,” a paper co-authored by researchers at NCI/FDA, Correlogic’s Chief Science Officer Ben Hitt, and others.  This research, including the continued use of Correlogic’s technology, was a further extension our previously reported ovarian cancer results, and showed results that were 100 percent sensitive and specific across all stages.

In its March/April 2004 issue, the peer-reviewed journal Toxicologic Pathology, published “Toxicoproteomics: Serum Proteomic Pattern Diagnostics for Early Detection of Drug Induced Cardiac Toxicities and Cardioprotection” a paper co-authored by Correlogic’s Chief Science Officer Ben Hitt, researchers at the NCI/FDA, and others.  This research is the first application of Correlogic’s pattern recognition approach and technology to drug toxicity — a significant issue in disease treatment.  Scientists identified patterns in mass spectra from sera that could identify rats treated with the cardiotoxic drug doxorubicin alone from those treated with doxorubicin and a cardioprotectant.  These results suggest that, using Correlogic’s technologies, such toxicities may be detectable before adverse effects become irreversible.

In December 2003, the peer-reviewed journal Cancer Cell, published “Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse”, a paper co-authored by Correlogic’s Chief Science Officer, Ben Hitt, along with researchers at NCI/FDA and others. This study, using mouse models, utilized Correlogic’s technology to detect pancreatic cancer. It was a demonstration of the applicability of our technology to another cancer — one in which the disease’s typically rapid progression makes early detection particularly important.

On October 16, 2002, the Journal of the National Cancer Institute published “Serum Proteomic Patterns for Detection of Prostate Cancer,” a study conducted by Correlogic and NCI/FDA applying Correlogic’s pattern discovery technology to successfully detect protein patterns rather than individual biomarkers for prostate cancer. From a single drop of blood, researchers were able to detect 95 percent of prostate cancer cases and rule out prostate cancer for 71 percent of men with intermediate PSA scores.
Press Release

On February 8, 2002, The Lancet released “Use of Proteomic Patterns in Serum to Identify Ovarian Cancer,” a study co-authored by Dr. Ben Hitt and Peter Levine of Correlogic and colleagues from National Cancer Institute and others. The study employed Correlogic proprietary technology in detecting ovarian cancer. Press Release