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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

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Page 1: Nonlinear gene activity- drug sensitivity relationship ... · positives. Our regression detector outperformed the correlation coefficient detector only on very small datasets. Keywords

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

Page 2: Nonlinear gene activity- drug sensitivity relationship ... · positives. Our regression detector outperformed the correlation coefficient detector only on very small datasets. Keywords

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

Page 3: Nonlinear gene activity- drug sensitivity relationship ... · positives. Our regression detector outperformed the correlation coefficient detector only on very small datasets. Keywords
Page 4: Nonlinear gene activity- drug sensitivity relationship ... · positives. Our regression detector outperformed the correlation coefficient detector only on very small datasets. Keywords

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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