Molecular Data Science: from disease mechanisms to personalized medicine

Focus of the course: Molecular Epidemiology in Ageing research

Biomedical research increasingly involves the generation and analysis of very large data sets whether it is whole-genome DNA sequencing, gene expression or magnetic resonance imaging data. In particular, large-scale data will be the cornerstone of personalized medicine. This course is aimed at biomedical students who not only want to be responsible for the generation of large-scale data in their future projects, but also want to be able to analyse and interpret their own data.

Literature and documents for study assignments will be handed out during the course.

Coordinators

Bas Heijmans, Molecular Epidemiology; 071-526 69785, [email protected]

Ingrid Meulenbelt, Molecular Epidemiology; 071-526 9734, [email protected]

Location

Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden: room J1-84 at the main building. For the practicals, computers in J1-84 will be used.

Storing valuables

Store valuables, especially during breaks, in one of the lockers available for library users, located on the left of the library entrance.

Assessment plan

• Handing in assignments (Pass/Fail, individually assessed).
• Contribute to interim evaluation of student participation and development during workgroups (0%).
• Fill out project proposal form as preparation for reflective assignment (0%).
• Presentation project proposal (background, hypothesis, pilot data, objectives, study design, workplan, expected outcomes; 45%, assessed in duos).
• Active and critical participation during discussion after project presentations of peers (15%, individually assessed).
• Reflective assignment that shows mastering key aspects of development of research proposal in molecular data science and addressing points raised during peer review (40%, individually assessed).

Overall the evaluation will be a score between 0-10 composed of a weighted average of the different modules.

Evaluation

For individual evaluation of students, the module coordinators of the first 2 weeks will judge the following:

• participation in the (paper) discussions
• answers to the questions in the practicals

The module coordinators of the third week will judge the following:

• written project proposal
• oral project defense

Overall the evaluation will be a score between 0-10 composed of a weighted average of the different modules.

PART 1 Acquiring knowledge and skills

Knowledge with respect to complex diseases and the different study designs available to investigate. In the practicals students will acquire skills (bioinformatic and statistical tools) how large datasets of genetic, gene expression and phenotypic data are analysed for pattern recognition in the data and to match results with existing biological information and to form new hypotheses.

WEEK 1

Monday October 22 (Location J1-84/building 1, LUMC)

When	What: Introduction to Molecular Epidemiology & R	Who	Where
9.00-9.45	Lecture: Introduction to FOS course	Bas Heijmans	J1-84
9.45-11.00	Lecture: Introduction to Molecular Epidemiology, large scale datasets	Eline Slagboom	J1-84
10.30-10.40	Coffee break + questions
11.00-11.45	Lecture: Introduction to large scale datasets; from SPSS to R	Bas Heijmans	J1-84
12.00-13.00	Lunch
13.00-15.00	Lecture: Introduction to R	Koen Dekkers	J1-84
13.00-15.00	Practical: Introduction to R	Koen Dekkers	J1-84
15.00-15.15	Tea break
15.15-17.00	Practical: Introduction to R	Koen Dekkers	J1-84

Tuesday October 23 (Location J1-84/building 1, LUMC)

When	What: Transcriptomics	Who	Where
9.00-10.00	Lecture: Introduction to Transcriptomics	Rodrigo C de Almeida and Yolande Ramos	J1-84
10.00-10.15	Coffee break
10.15-12.30	Practicals: Statistical analysis of RNA-seq data: Normalization, differential expression and multiple testing	Rodrigo C de Almeida and Yolande Ramos	J1-84
12.30-13.30	Lunch
13.30-14.15	Lecture: Finding functional relevant genes	Yolande Ramos and Rodrigo C de Almeida	J1-84
14.15-15.00	Lecture: Finding genes in practice	Yolande Ramos and Rodrigo C de Almeida	J1-84
15.00-15.15	Tea Break
15.15-17.00	Practical: Finding genes in practice cont'd	Yolande Ramos and Rodrigo C de Almeida	J1-84

Wednesday October 24 (Location J1-84/building 1, LUMC)

When	What: Genetics	Who	Where
9.00-10.00	Lecture: Introduction to Genome-wide association	Marian Beekman	J1-84
10.00-10.15	Coffee break
10.15-12.00	Lecture and Practical: Genome-wide association	Marian Beekman	J1-84
12.00-13.00	Lunch
13.00-15.00	Lecture and Practical: Genome-wide association	Marian Beekman	J1-84
15.00-15.15	Tea break
15.30-16.30	Lecture and Practical: Genome-wide association	Marian Beekman	J1-84
16.30-17.00	Interim evaluation of participation and interaction	Bas Heijmans	J1-84

Thursday October 25 (Location morning: J1-83 / Afternoon: J1-84/building 1, LUMC)

When	What: post-GWAs functional follow up	Who	Where
9.00-10.00	Self-study: Freedman et al. (2011) Principles for the post-GWAS functional characterization	Ingrid Meulenbelt	J1-83
10.00-10.15	Coffee Break
10.15-10.30	Self-study: Freedman et al. continued	Self	J1-83
10.30-11.30	Paper discussion: Freedman et al.	Ingrid Meulenbelt	J1-83
10.30-11.30	Paper discussion: Freedman et al.	Ingrid Meulenbelt	J1-83
11.30-12.00	Lecuture: Functional genomics	Ingrid Meulenbelt	J1-83
12.00-13.00	Lunch
When	What: DNA Methylomics	Who	Where
13.00-14.00	Lecture: Introduction to the epigenome	Bas Heijmans and Roderick Slieker	J1-84
14.00-15.15	Practical: Tissues & 450K methylation chip data	Roderick Slieker	J1-84
15.15-15.30	Tea Break
15.30-17.00	Practical: Tissues & 450K methylation chip data cont'd	Roderick Slieker	J1-84

Friday October 26 (Location J1-84/building 1, LUMC)

When	What: DNA Methylomics	Who	Where
9.00-10.00	Practical: Tissues & 450K methylation chip data cont'd	Roderick Slieker	J1-84
10.00-10.15	Coffee Break
10.15-11.30	Practical: Tissues & 450K methylation chip data cont'd	Roderick Slieker	J1-84
11.30-12.30	Lecture: DNA methylation signatures of prenatal famine exposure	Bas Heijmans	J1-84
12.30-13.30	Lunch
When	What: Ageing biomarkers; clocks of chronological and biological age	Who	Where
13.30-15.30	Lecture: Metabolomics as biomarkers	Eline Slagboom	J1-84
	Self-study; Marioni et al. (2016) The epigenetic clock and telomere length are independently associated with chronological age and mortality	Self	J1-84
15.00-15.15	Coffee Break
15.15-17.00	Paper discussion: Marioni et al.	Eline Slagboom	J1-84

WEEK 2

Monday October 29 (Location J1-84/building 1, LUMC)

When	What: Metabolomics	Who	Where
9.00-10.00	Lecture: Introduction to metabolomics	Marian Beekman and Erik van den Akker	J1-84
10.00-10.15	Coffee Break
10.15-12.30	Practical: Metabolomics practical	Marian Beekman and Erik van den Akker	J1-84
12.30-13.30	Lunch
When	What: Integrative approaches	Who	Where
13.30-14.00	Lecture: Integrated analysis of multiple –omics data and Mendelian randomization	Bas Heijmans	J1-84
14.00-15.00	Practical: Hands on Integration of –omics datasets;eQTL, mQTL, Mendelian Randomization	Bas Heijmans and Koen Dekkers	J1-84
15.00-15.15	Tea Break		J1-82
15.15-17.00	Practical: Hands on Integration of –omics datasets;eQTL, mQTL, Mendelian Randomization	Bas Heijmans and Koen Dekkers	J1-84

Tuesday October 30 (Location J1-84/building 1, LUMC)

When	What: Next generation sequencing	Who	Where
9.00-9.45	Lecture: Next generation sequencing technology	Susan Kloet	J1-84
9.45-11.00	Lab tour Next generation sequencing technology	Susan Kloet	Building 2
11.00-11.15	Coffee Break
11.15-12.00	Lecture: Medical sequencing (principles exome and WGA sequencing)	Ingrid Meulenbelt	J1-84
12.00-13.00	Lunch
13.00-13.15	Interim evaluation of participation and interaction	Bas Heijmans	J1-84
13.15-15.00	Practical: Exome sequencing early onset OA	Ingrid Meulenbelt and Yolande Ramos	J1-84
15.00-15.15	Tea Break
15.15-17.00	Practical continued: Exome sequencing early onset OA	Ingrid Meulenbelt and Yolande Ramos	J1-84

Wednesday October 31 (Location J1-84/building 1, LUMC)

When	What: Single cell RNA-sequencing & clustering	Who	Where
9.00-10.00	Lecture: Single cell RNA-sequencing	Ahmed Mahfouz	J1-84
10.00-10.15	Coffee Break
10.15-12.00	Practical: Single cell RNA-sequencing	Indu Khatri, Ahmed Mahfouz	J1-84
12.00-13.00	Lunch
When	What: Clustering analysis	Who	Where
13.00-15.00	Lecture: Clustering analysis transcriptomic data	Marcel Reinders	J1-84
15.00-15.15	Tea Break
15.15-17.00	Practical: Clustering analysis transcriptomic data	Marcel Reinders	J1-84

Thursday November 1 (Location J1-84/building 1, LUMC)

When	What: Databases reproducibility	Who	Where
9.00-10.30	Lecture: GONL, BIOS, UK biobank, GTEX, reproducibility	Bas Heijmans	J1-84
10.30-10.45	Coffee Break
10.45 -12.00	Practical: Online databases exploration	Roderick Slieker	J1-84
12.00-13.00	Lunch
When	What: Animal models on ageing	Who	Where
13:00-13:30	Lecture	Vered Raz	J1-84
13:30-16:00	Self study on papers in groups	Vered Raz	J1-84
15:00-15:15	Tea Break
16:00-17:00	Presentation of papers by groups	Vered Raz	J1-84

PART 2. Applying acquired knowledge and skill to ageing.

Students will apply newly acquired competences to write a research proposal that follows a data science approach to study ageing as a key example of a complex human trait. Students will work on developing a project proposal in duos. Generating pilot data by analyzing available ‘real’ omics data sets to support hypotheses will be an integral part of the project proposal. During the week there will be regular moments of interaction with the module coordinators and the possibility to contact other tutors of the course.

Friday November 2 (Location J1-84/building 1, LUMC)

When	What: Introduction to Developing Project Proposal	Who	Where
9.00-10.00	Project proposal: where does research start. Part 1	Eline Slagboom	J1-84
10.00-10.15	Coffee Break
10.15-11.00	Project proposal: where does research start. Part 2	Eline Slagboom	J1-84
11.00-12.00	Work on the project proposal: formulation of hypothesis	Self	J1-84
12.00-13.00	Lunch and self study
13.00-17.00	Work on the project proposal: formulation of objectives	Self	J1-84

Monday November 5 (Location J1-84/building 1, LUMC)

When	What: Final assignment	Who	Where
9.00-17.00	Work on the project proposal (J1-84)	Self	J1-84

Tuesday November 6 (Location J1-84/building 1, LUMC)

When	What: Final assignment	Who	Where
9.00-17.00	Work on the project proposal (J1-82)	Self	J1-84

Wednesday November 7 (Location J1-84/building 1, LUMC)

When	What: Final assignment	Who	Where
9.00-17.00	Work on the project proposal (J1-84)	Self	J1-84

Thursday November 8 (Location J1-84/building 1, LUMC)

When	What: Final assignment	Who	Where
9.00-12.30	Work on the project proposal (J1-84)	Self	J1-84
13.30-16.30	Oral presentation and defence of project proposal	All	S0-19
16.30-17.00	Looking back on course	All	S0-19

Friday November 9 (Location J1-84/building 1, LUMC)

When	What Final assignment	Who	Where
9.00-13.00	Self study	Self	J1-84
13.00-15.00	Reflective Assignment		J1-84
01:00:00 PM	End of course