Doctoral Thesis

Transcriptomic Characterization Using RNA-Seq Data Analysis

FEKTDoctoral ThesisStudent: Layal Abo Khayal, Ph.D.Acad. year: 2017/2018

Leader: prof. Ing. Ivo Provazník, Ph.D.

Opponents: prof. Pharm.Dr. Petr Babula, Ph.D., Ing. Matej Lexa, Ph.D.

The high-throughputs sequence technologies produce a massive amount of data, that can reveal new genes, identify splice variants, and quantify gene expression genome-wide. However, the volume and the complexity of data from RNA-seq experiments necessitate a scalable, and mathematical analysis based on a robust statistical model. Therefore, it is challenging to design integrated workflow, that incorporates the various analysis procedures. Particularly, the comparative transcriptome analysis is complicated due to several sources of measurement variability and poses numerous statistical challenges. In this research, we performed an integrated transcriptional profiling pipeline, which generates novel reproducible codes to obtain biologically interpretable results. Starting with the annotation of RNA-seq data and quality assessment, we provided a set of codes to serve the quality assessment visualization needed for establishing the RNA-Seq data analysis experiment. Additionally, we performed comprehensive differential gene expression analysis, presenting descriptive methods to interpret the RNA-Seq data. For implementing alternative splicing and differential exons usage analysis, we improved the performance of the Bioconductor package DEXSeq by defining the open reading frame of the exonic regions, which are differentially used between biological conditions due to the alternative splicing of the transcripts. Furthermore, we present a new methodology to analyze the differentially expressed long non-coding RNA, by finding the functional correlation of the long non-coding RNA with neighboring differential expressed protein coding genes. Thus, we obtain a clearer view of the regulation mechanism, and give a hypothesis about the role of long non-coding RNA in gene expression regulation.

Language

English

State

Defended (thesis was successfully defended)

Hodnocení známka

P

Faculty

Department

Study branch

Biomedical Electronics and Biocybernetics (PP-BEB)

Classification by leader
prof. Ing. Ivo Provazník, Ph.D.

Dissertation thesis Layal Abo Khayal is focused on the field of high-throughput sequence technologies that produce a massive amount of data to reveal new genes, identify splice variants, and quantify gene expression genome-wide. Based on the presented work, I can state that the author fulfilled the goals set in the dissertation thesis and achieved remarkable results in the field of development of methods for analysis of large volumes of data from RNA-Seq experiments. I consider as essential that the author found and validated a robust computational pipeline that improves results of existing tools. Most of her dissertation was developed during her stay at Charité – Universitätsmedizin Berlin in the past three years.
Layal Abo Khayal started her PhD study in 2010 and oriented to design and validation of intelligent methods, algorithms and pipelines for data processing and visualization in bioinformatics. She worked actively and aimed to achieve important results in bioinformatics. Based on her results, she was supported by South Moravian Centre For International Mobility during her study. Layal worked actively throughout her PhD studies and demonstrated the ability to develop independent creative work, including the ability to present the results. She achieved valuable results in the form of quality publications, including the publication of the core of the dissertation in an article in an impacted journal. I also appreciate the thorough and critical approach to evaluating her own results and trying to maximize verification through numerous in silico experiments, even though this prolonged finalization of her dissertation. I am convinced that Layal has developed a valuable dissertation and has reached the scientific level needed to award the Doctor degree.



Classification by opponent
prof. Pharm.Dr. Petr Babula, Ph.D.

viz příloha pdf



File inserted by the reviewer Size
Posudek disertační práce Layal Abo Khayal_prof. Babula.pdf 988.95 kB

Classification by opponent
Ing. Matej Lexa, Ph.D.

viz příloha pdf



File inserted by the reviewer Size
Posudek oponenta Dr. Lexa_Layal Abo Khayal.pdf 654.4 kB

Keywords

RNA-Seq, Differential Gene Expression (DGE), Alternative splicing, Differential Exon Usage (DEU), long non-coding RNA (lncRNA).

Reason for concealment

The publication of the dissertation is deferred in accordance with the provision of § 47b (4) of Act No. 111/1998 Coll., On Higher Education Institutions. The reason for the postponement of the publication is the fact that the dissertation contains information protected by special legal regulations (eg No. 527/1990 Coll., On Inventions and Improvement Proposals).