Research issues and strategies for genomic and proteomic biomarker discovery and validation: a statistical perspective

Pharmacogenomics
Ziding FengSudir Srivastava

Abstract

The development and validation of clinically useful biomarkers from high-dimensional genomic and proteomic information pose great research challenges. Present bottlenecks include: that few of the biomarkers showing promise in initial discovery were found to warrant subsequent validation; and biomarker validation is expensive and time consuming. Biomarker evaluation should proceed in an orderly fashion to enhance rigor and efficiency. A molecular profiling approach, although promising, has a high chance of yielding biased results and overfitted models. Specimens from cohorts or intervention trials are essential to eliminate biases. The high cost for biomarker validation motivates some novel study design features, including sequential filtering and DNA pooling. For data analysis, logistic regression (in particular, boosting logistic regression) has features of robustness against model misspecification, and has resistance to model overfitting. Model assessment and cross-validation are critical components of data analysis. Having an independent test set is a vital feature of study design.

References

Aug 27, 1998·Journal of the National Cancer Institute·A ShibataA S Whittemore
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Jul 19, 2001·Journal of the National Cancer Institute·M S PepeY Yasui
Dec 1, 2001·Nucleic Acids Research·G NallurB Schweitzer
Feb 2, 2002·Nature·Laura J van 't VeerStephen H Friend
Feb 28, 2002·Lancet·Emanuel F PetricoinLance A Liotta
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Frank B DeanRoger S Lasken
Sep 17, 2002·Biometrics·Martin W McIntosh, Margaret Sullivan Pepe
Nov 5, 2002·Nature Reviews. Genetics·Pak ShamMichael Owen
Dec 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Karen L MohlkeFrancis S Collins
Dec 20, 2002·The New England Journal of Medicine·Marc J van de VijverRené Bernards
Jan 2, 2003·Journal of the National Cancer Institute·Richard SimonLisa M McShane
Apr 16, 2003·Annals of Internal Medicine·Mitchell H Katz
May 24, 2003·Biometrics·Margaret Sullivan PepeMichel Schummer
Dec 20, 2003·Nature·UNKNOWN International HapMap Consortium
Mar 5, 2004·Journal of the National Cancer Institute·Eleftherios P Diamandis
Apr 2, 2004·Nature Reviews. Cancer·David F Ransohoff
May 28, 2004·The New England Journal of Medicine·Ian M ThompsonCharles A Coltman
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Robert J Tibshirani, Brad Efron

❮ Previous
Next ❯

Citations

Aug 4, 2006·Molecular Diagnosis & Therapy·Sudhir Srivastava
Oct 19, 2007·Lifetime Data Analysis·Duncan C Thomas
Jun 8, 2012·Journal of General Internal Medicine·Thomas S RectorTimothy J Wilt
Jan 24, 2008·European Journal of Human Genetics : EJHG·Jennifer A SmithSharon L R Kardia
Mar 13, 2009·Human Reproduction Update·Sun-Wei Guo
Oct 9, 2008·Journal of the National Cancer Institute·Margaret S PepeJohn D Potter
Oct 9, 2008·Journal of the National Cancer Institute·David F Ransohoff
Sep 16, 2011·Advances in Dental Research·B J BaumJ E Melvin
Jun 15, 2011·Clinical Chemistry·Margaret S Pepe, Ziding Feng
May 6, 2011·Proceedings of the American Thoracic Society·Mohamed HassaneinPierre P Massion
Oct 28, 2008·Biological Chemistry·Marc JacobsenStefan H E Kaufmann
Mar 29, 2014·Journal of Hypertension·Sonja B NikolicLindsay M Edwards
Dec 24, 2013·Biochimica Et Biophysica Acta·B PeschT Behrens
Nov 13, 2015·Expert Review of Proteomics·Claudia FredoliniJochen M Schwenk
Jan 22, 2013·Expert Opinion on Medical Diagnostics·Jason E McDermottKarin D Rodland
Mar 29, 2011·Critical Care Clinics·Brian CasserlyMitchell M Levy
Nov 17, 2010·Human Pathology·Nam K YoonLee Goodglick
Dec 10, 2009·Journal of Proteomics·David S GibsonMadeleine E Rooney
Nov 14, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ana Villar-GareaAxel Imhof
Aug 5, 2009·Rapid Communications in Mass Spectrometry : RCM·Simone CristoniPietro Traldi
May 14, 2009·Rapid Communications in Mass Spectrometry : RCM·Paolo LecchiJohn M Peltier
Jan 13, 2006·Biometrics·Ross L PrenticeGarnet L Anderson
Dec 8, 2010·Proteomics. Clinical Applications·Cedric WiesnerKeith Wilson
Jul 23, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·Peter A LewittUNKNOWN Arizona Parkinson's Disease Consortium
Apr 25, 2012·Biotechnology Journal·Jaeyun SungNathan D Price
Jan 15, 2014·Biochimica Et Biophysica Acta·Shabarni GuptaSanjeeva Srivastava
Jun 29, 2013·Biochimica Et Biophysica Acta·Andrew J PercyChristoph H Borchers
Jul 19, 2005·Drug Discovery Today·Upender ManneSudhir Srivastava
Mar 17, 2009·Neurobiology of Disease·Clemens R Scherzer
Nov 6, 2013·Autoimmunity Reviews·Sunil MahurkarCatherine O'Doherty
Jan 1, 2011·Cancers·Mukesh VermaMudit Verma
Sep 23, 2014·World Journal of Methodology·Florin-Dan Popescu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.