nonlinear gene activity- drug sensitivity relationship ... · positives. our regression detector...
TRANSCRIPT
UPTEC X 05 021 ISSN 1401-2138 APR 2005
KARIN HOLMSTRÖM
Nonlinear gene activity- drug sensitivity relationship modelling for improved detection of genes that affect drug sensitivity Master’s degree project
Molecular Biotechnology Programme Uppsala University School of Engineering
UPTEC X 05 021 Date of issue 2005-04 Author
Karin Holmström Title (English)
Nonlinear gene activity–drug sensitivity relationship modelling for improved detection of genes
that affect drug sensitivity Abstract A novel approach for detection of genes whose products affect drug sensitivity wasintroduced. Two detectors, one based on nonlinear regression and the other on errors invariable modelling, have been tested on simulated data and was, using reciever operatingcharacteristics graphs, compared to a linear state-of-the-art detection strategy, which is based on Pearson's correlation coefficient. On small and nonlinear datasets our modelling detectorperformed significantly better than the correlation coefficient detector. For example, a datasetsize of five points gave under certain circumstances a rate of true positives of the modellingdetector that was four times that of the correlation coefficient detector, both at 5% false positives. Our regression detector outperformed the correlation coefficient detector only onvery small datasets. Keywords Relationship modelling, regression, drug sensitivity, correlation coefficient, detection. Supervisors
Mats Gustafsson Dept. of Engineering Sciences, Uppsala University
Scientific reviewer
Anders Isaksson Dept. of Genetics and Pathology, Uppsala University
Language
English
Security
ISSN 1401-2138
Classification
Supplementary bibliographical information Pages 22
Biology Education Centre Biomedical Center Husargatan 3 Uppsala Box 592 S-75124 Uppsala Tel +46 (0)18 4710000 Fax +46 (0)18 555217
Nonlinear gene activity–drug sensitivity relationship modelling for improved detection of genes that affect drug sensitivity
Karin Holmström
Sammanfattning
Läkemedelskänslighet, d v s hur stark effekt ett läkemedel har, varierar från patient till patient. Detta är ett problem vid t ex kemoterapi i behandling av cancer. Men denna variation kan utnyttjas för att hitta gener som påverkar just läkemedelskänsligheten. Kännedom om patientens uttrycksnivåer av dessa gener kan användas vid individuell behandling och för att förutsäga behandlingens slagkraft. Dessa gener kan också ge information om hur olika läkemedel fungerar. Om man känner till patienters läkemedelskänslighet och uttrycksnivåer för olika gener kan man identifiera de intressanta generna på olika sätt. Tidigare har en korrelationskoefficient mellan genuttryck och läkemedelskänslighet använts som mått på hur mycket genen påverkar läkemedelskänsligheten. Denna metod vore smidig och bra om sambandet mellan genuttryck och läkemedelskänslighet vore linjärt. Emellertid är detta inte fallet och i detta projekt har data istället anpassats till en ickelinjär kurva på två olika sätt. Dessa metoder för att hitta gener har med hjälp av simulerade data testats och jämförts med korrelationskoefficientmetoden. Det visade sig att de nya metoderna generellt sett presterar bättre när man har små datamängder.
Examensarbete 20 p civilingenjörsprogrammet i molekylär bioteknik Uppsala universitet, april 2005
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