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Zebrash larva action sequence analysis

Mislej, Jerneja (2017) BINP41 20162
Degree Projects in Bioinformatics
Abstract
Zebrafish larvae action sequences were analysed in order to compare and profile several different drugs for therapeutic purposes in neurological diseases.
Healthy and neurological disease induced larvae were treated with different drugs and drug dosages and their movement recorded into action sequences. Action sequences were categorized into eight different turn types and organised in swim bouts. Descriptive statistics, derived from bout length, bout frequency, distribution of turns and turn transitions, can be linked to the larval neurological state.
The master thesis project focused on the design, implementation and testing of potential analysis pipelines which could provide insight into the effects of the various drugs and their... (More)
Zebrafish larvae action sequences were analysed in order to compare and profile several different drugs for therapeutic purposes in neurological diseases.
Healthy and neurological disease induced larvae were treated with different drugs and drug dosages and their movement recorded into action sequences. Action sequences were categorized into eight different turn types and organised in swim bouts. Descriptive statistics, derived from bout length, bout frequency, distribution of turns and turn transitions, can be linked to the larval neurological state.
The master thesis project focused on the design, implementation and testing of potential analysis pipelines which could provide insight into the effects of the various drugs and their dosages on the larval neurological state. By conducting an exploratory PCA, various drugs and drug dosages were compared in their effect on the neurological state of the healthy and disease induced larvae, while direct effects on the most influential descriptive statistics were obtained with a generalized linear mixed effects model with reference to the healthy larvae. (Less)
Popular Abstract
Analysis of zebrafish swim turns

Zebrafish larvae swim turns, recorded into action sequences, were analysed in order to compare and profile several different drugs for therapeutic purposes in neurological diseases.
The master thesis project focused on the design, implementation and testing of potential analysis pipelines which could provide insight into the effects of the various drugs and their dosages on the larval neurological state, represented with the information extracted from zebrafish larvae swim patterns.

The larval zebrafish animal model enables a more profound and accurate drug screening process, since it combines the advantages of cell-based high-throughput screening techniques and whole organism phenotype data.
In... (More)
Analysis of zebrafish swim turns

Zebrafish larvae swim turns, recorded into action sequences, were analysed in order to compare and profile several different drugs for therapeutic purposes in neurological diseases.
The master thesis project focused on the design, implementation and testing of potential analysis pipelines which could provide insight into the effects of the various drugs and their dosages on the larval neurological state, represented with the information extracted from zebrafish larvae swim patterns.

The larval zebrafish animal model enables a more profound and accurate drug screening process, since it combines the advantages of cell-based high-throughput screening techniques and whole organism phenotype data.
In the current project, healthy and neurological disease induced larvae were treated with different drugs and drug dosages and their swim turns recorded into action sequences, organised in swim bouts. Information, derived from bout length, bout frequency, distribution of turns and turn transitions, can be linked to the larval neurological state, with the lack of published studies focusing on turns and turn transitions.
By analysing and comparing the extracted information, including turns and turn transitions performed by healthy individuals and individuals with a neurological condition, medication target and off-target effects could be identified and analysed more accurately.

Several zebrafish action sequence preprocessing and analysis pipelines were designed, implemented and tested, including data filtering, information extraction, comparative exploratory data analysis and mixed effects analysis.

Successful data filtering was achieved with a model of manually detected technical outliers, which enabled an automatic detection of the remaining outliers.
Swim bout count and swim bout length variables influenced the overall proportion of turns and turn transitions, where turn transitions were additionally influenced by the turn proportions. Characteristics of the extracted information was taken in to account when designing the analysis pipeline.

Exploratory data analysis showed several trends in changes through time and through dosage for the different drugs given to the healthy and neurological disease induced larvae, enabling identification of drugs and drug dosages with target and off-target effects.

In the final steps of the analysis, direct drug and drug dosage effects on the turn and turn transitions were obtained and analysed. The information regarding changes in turns and turn transitions provided additional insight into the zebrafish larval neurological behaviour and therefore improved the profiling of drugs for therapeutic purposes in neurological diseases.

Master’s Degree Project in Bioinformatics 30 credits 2017
Department of Biology, Lund University

Supervisor: Fredrik Ek, Chemical Biology and Therapeutics, Department of Experimental Medical Science, Faculty of Medicine
Co-supervisors: Mauno Vihinen, Protein Structure and Bioinformatics, Department of Experimental (Less)
Please use this url to cite or link to this publication:
author
Mislej, Jerneja
supervisor
organization
course
BINP41 20162
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8928692
date added to LUP
2017-11-22 16:05:53
date last changed
2017-11-22 16:05:53
@misc{8928692,
  abstract     = {Zebrafish larvae action sequences were analysed in order to compare and profile several different drugs for therapeutic purposes in neurological diseases. 
Healthy and neurological disease induced larvae were treated with different drugs and drug dosages and their movement recorded into action sequences. Action sequences were categorized into eight different turn types and organised in swim bouts. Descriptive statistics, derived from bout length, bout frequency, distribution of turns and turn transitions, can be linked to the larval neurological state.
The master thesis project focused on the design, implementation and testing of potential analysis pipelines which could provide insight into the effects of the various drugs and their dosages on the larval neurological state. By conducting an exploratory PCA, various drugs and drug dosages were compared in their effect on the neurological state of the healthy and disease induced larvae, while direct effects on the most influential descriptive statistics were obtained with a generalized linear mixed effects model with reference to the healthy larvae.},
  author       = {Mislej, Jerneja},
  language     = {eng},
  note         = {Student Paper},
  title        = {Zebrash larva action sequence analysis},
  year         = {2017},
}