Computation and Selection of Optimal Biomarker Combinations by Integrative ROC Analysis Using CombiROC

AbstractBacterial culture of M. tuberculosis (MTB), the causative agent of tuberculosis (TB), from clinical specimens is the gold standard for laboratory diagnosis of TB, but is slow and culture-negative TB cases are common. Alternative immune-based and molecular approaches have been developed, but cannot discriminate between active TB (ATB) and latent TB (LTBI). Here, to identify biomarkers that can discriminate between ATB and LTBI/healthy individuals (HC), we profiled 116 serum samples (HC, LTBI and ATB) using a protein microarray containing 257 MTB secreted proteins, identifying 23 antibodies against MTB antigens that were present at significantly higher levels in patients with ATB than in those with LTBI and HC (Fold change > 1.2; p < 0.05). A 4-protein biomarker panel (Rv0934, Rv3881c, Rv1860 and Rv1827), optimized using SAM and ROC analysis, had a sensitivity of 67.3% and specificity of 91.2% for distinguishing ATB from LTBI, and 71.2% sensitivity and 96.3% specificity for distinguishing ATB from HC. Validation of the four candidate biomarkers in ELISA assays using 440 serum samples gave consistent results. The promising sensitivity and specificity of this biomarker panel suggest it merits further investigation for its potential as a diagnostic for discriminating between latent and active TB.

Download Full-text

Practical Issues of Experimental ROC Analysis Selection of Controls

Investigative Radiology ◽

10.1097/00004424-199005000-00019 ◽

1990 ◽

Vol 25 (5) ◽

pp. 583-586 ◽

Cited By ~ 16

Author(s):

DAVID GUR ◽

JILL L. KING ◽

HOWARD E. ROCKETTE ◽

CYNTHIA A. BRITTON ◽

F. LELAND THAETE ◽

...

Keyword(s):

Roc Analysis ◽

Selection Of

Download Full-text

Is Divorce Predictable among Iranian Couples?

Canadian Journal of Family and Youth / Le Journal Canadien de Famille et de la Jeunesse ◽

10.29173/cjfy29500 ◽

2020 ◽

Vol 12 (1) ◽

pp. 243-259

Author(s):

Gholamhosein Shahraki ◽

Zahra Sedaghat ◽

Mohammad Fararouei ◽

Zibaneh Tabeshfar

Keyword(s):

Family Relationships ◽

Roc Analysis ◽

Case Control Study ◽

Multivariable Analysis ◽

Married Couples ◽

Health Concern ◽

Public Health Concern ◽

Iranian Family ◽

Control Study ◽

Selection Of

Divorce is considered as an important social and public health concern worldwide. The aim of this study was to identify divorce’s social and economic contributors among Iranian couples. This case-control study was conducted on 60 divorced and their neighboring 64 still-married couples with approximately the same date of marriage. The required information was obtained from consultant administrated forms which are used routinely by Iranian family consulting centers. An interview-administered questionnaire with almost the same structure and questions was used to obtain information from still-married couples. Based on the results of multivariable analysis and (stepwise) selection of the study variables, significant associations between divorce and employment of both husbands and wives, education of husband, and the couple’s accommodation statuses were found. Accordingly, wife's (OR unemployed/self-employed=4.97, 95%CI: 1.38-21.61, P=0.001) and husband's (OR unemployed/self-employed =17.45, 95%CI: 3.56-123.98, P=0.001) unemployment, less educated husband's (OR primary or secondary/higher education =23.98, 95%CI=4.04-237.05, p=0.001) and couples with shared accommodation (OR dependent/independent= 5.99, 95%CI=2.54-17.72, P<0.001) were at higher risk of divorce. ROC analysis suggested that divorce can be confidently predicted by the above factors (AUC=0.882 95%CI: 0.816-0.948) with 66.7% sensitivity and 92.6% specificity. This study introduced several predictors, which can be used by family consultants and psychologists to recognize high risk marrying or married couples to prevent divorce and to help couples to obtain and sustain healthier marriages and stronger family relationships.

Download Full-text

Transcriptome analysis identifies putative multi-gene signature distinguishing benign and malignant pancreatic head mass

Journal of Translational Medicine ◽

10.1186/s12967-020-02597-1 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Bishnupriya Chhatriya ◽

Moumita Mukherjee ◽

Sukanta Ray ◽

Barsha Saha ◽

Somdatta Lahiri ◽

...

Keyword(s):

Roc Analysis ◽

Correct Diagnosis ◽

Pancreatic Head ◽

Gene Signature ◽

Rt Pcr ◽

Head Region ◽

Genome Wide ◽

Potential Biomarker ◽

Control Study ◽

Selection Of

Abstract Background Most often, the patients with pancreatic diseases are presented with a mass in pancreatic head region and existing methods of diagnosis fail to confirm whether the head mass is malignant or benign. As subsequent management of the disease hugely depends on the correct diagnosis, we wanted to explore possible biomarkers which could distinguish benign and malignant pancreatic head masses. Methods In order to address that gap, we performed a case–control study to identify genome-wide differentially expressed coding and noncoding genes between pancreatic tissues collected from benign and malignant head masses. These genes were next shortlisted using stringent criteria followed by selection of top malignancy specific genes. They subsequently got validated by quantitative RT-PCR and also in other patient cohorts. Survival analysis and ROC analysis were also performed. Results We identified 55 coding and 13 noncoding genes specific for malignant pancreatic head masses. Further shortlisting and validation, however, resulted in 5 coding genes as part of malignancy specific multi-gene signature, which was validated in three independent patient cohorts of 145 normal and 153 PDAC patients. We also found that overexpression of these genes resulted in survival disadvantage in the patients and ROC analysis identified that combination of 5 coding genes had the AUROC of 0.94, making them potential biomarker. Conclusions Our study identified a multi-gene signature comprising of 5 coding genes (CDCA7, DLGAP5, FOXM1, TPX2 and OSBPL3) to distinguish malignant head masses from benign ones.

Download Full-text

Discordance Analysis Characteristics as a New Method to Compare the Diagnostic Accuracy of Tests: Example of Complexed Versus Total Prostate-Specific Antigen

Clinical Chemistry ◽

10.1373/clinchem.2004.039552 ◽

2005 ◽

Vol 51 (3) ◽

pp. 532-539 ◽

Cited By ~ 7

Author(s):

Thomas Keller ◽

Hermann Butz ◽

Michael Lein ◽

Maciej Kwiatkowski ◽

Axel Semjonow ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Prostate Specific Antigen ◽

Roc Analysis ◽

Specific Antigen ◽

Roc Curve Analysis ◽

Data Set ◽

New Approach ◽

Additional Tool ◽

Total Prostate Specific Antigen ◽

Selection Of

Abstract Background: ROC curve analysis is used to compare the overall diagnostic accuracy of tests, but its application to subgroups selected by a concentration range of only one marker may show severe biases. We developed a new approach, which we have named discordance analysis characteristics (DAC). Methods: The DAC method is based on a generalization of the McNemar test so that for a given pair of cutoff values only those patients are analyzed who are categorized differently by the two tests compared. The analyses are performed for all cutoff pairs that deliver identical sensitivities for both tests. We used data for total (tPSA) and complexed prostate-specific antigen (cPSA) from a recently published multicenter study to demonstrate the DAC method. Results: The example shows that ROC analyses of subgroups can give contradictory results about the diagnostic accuracy of two markers, depending on the marker used for the selection of subgroups. The DAC method avoids artifacts attributable to questionable selection of subgroups and facilitates overall and local comparisons of the diagnostic accuracy of tests. The DAC results of the analyzed data set suggest that cPSA has higher diagnostic accuracy than does tPSA. Conclusions: The DAC method is a suitable tool for comparing the clinical usefulness of laboratory markers. The DAC method could be considered as an additional tool to ROC analysis and could replace comparative ROC analyses of diagnostic tests, especially within subgroups defined by only one of the markers.

Download Full-text

Cognitive gadgets and cognitive priors

Behavioral and Brain Sciences ◽

10.1017/s0140525x19000992 ◽

2019 ◽

Vol 42 ◽

Author(s):

Gian Domenico Iannetti ◽

Giorgio Vallortigara

Keyword(s):

Cognitive Neuroscience ◽

Selection Of

Abstract Some of the foundations of Heyes’ radical reasoning seem to be based on a fractional selection of available evidence. Using an ethological perspective, we argue against Heyes’ rapid dismissal of innate cognitive instincts. Heyes’ use of fMRI studies of literacy to claim that culture assembles pieces of mental technology seems an example of incorrect reverse inferences and overlap theories pervasive in cognitive neuroscience.

Download Full-text

Note on Selection of Coordinate Systems for Geodynamics

International Astronomical Union Colloquium ◽

10.1017/s0252921100051174 ◽

1975 ◽

Vol 26 ◽

pp. 395-407

Author(s):

S. Henriksen

Keyword(s):

Sea Level ◽

The Other ◽

Coordinate Systems ◽

Mean Sea Level ◽

The Earth ◽

The One ◽

Static Systems ◽

Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

Download Full-text

Measurements of the Cape Astrometric Survey of the Southern Hemisphere

International Astronomical Union Colloquium ◽

10.1017/s0252921100074534 ◽

1978 ◽

Vol 48 ◽

pp. 515-521

Author(s):

W. Nicholson

Keyword(s):

Southern Hemisphere ◽

Automatic Measuring ◽

Measuring Machine ◽

Final Selection ◽

Selection Of

SummaryA routine has been developed for the processing of the 5820 plates of the survey. The plates are measured on the automatic measuring machine, GALAXY, and the measures are subsequently processed by computer, to edit and then refer them to the SAO catalogue. A start has been made on measuring the plates, but the final selection of stars to be made is still a matter for discussion.

Download Full-text