Bioinformatics

The course includes 48 hours of theoretical lectures, computer exercises and student seminars. Molecular Biology (24 hours) The genome and the functional complexity of eukaryotes. RNA maturation: capping, splicing and polyadenylation. Alternative splicing as a mechanism to increase functional complexity; Splicing regulation and gene therapy (Duchenne Muscular Dystrophy); RNA export and stability; Chromatin structure and histone modifications; the “mRNA Factory”: coupling between transcriptional and post-transcriptional processes; Non coding RNAs: RNA interference: discovery, mechanism of action and factors; microRNAs (miRNAs): biogenesis, mechanism of action and role in cell differentiation and proliferation; long non-coding RNAs (lncRNAs): nuclear and cytoplasmic species (biogenesis and function); circular RNAs (circRNAs): biogenesis and function; RNAi and chromatin. Structural Genomics (12 hours). Evolution of the concept of gene: from Darwin's theories of heredity to the post-genomic era; the Human Genome Project. The Encode project. DNA (Sanger method, Maxam-Gilbert, BAC) and genome sequencing technologies. Automated sequencing. The Next-Generation Sequencing (NGS). The "Illumina" technology. Anatomy of genomes, genome size and number of genes. The non-coding DNA (ncDNA). RNA sequencing technologies. The transcriptome and high-throughput analysis of gene expression; WET lab and DRYLAB for a typical RNA-seq analysis (FASTQ, PHRED quality score, FASTQC). De-novo identification and differential expression analysis of mRNA and non-coding RNAs (ncRNA). Genetic and biochemical approaches to the study of the Interactome. The yeast two-hybrid system. Immunoprecipitation, Co-immunoprecipitation, Protein tagging and pull-down assays. Studying the interaction between PROTEIN (ChIP) and RNA (ChIRP) with the chromatin: the i) Chromatin Immunoprecipitation (ChIP) and the ii) Chromatin Isolation by RNA Purification (ChIRP). Identification and study of sub-topological domains (TADs). 3C, 5C, Hi-C e ChIA-PET. Functional Genomics (6 hours). Forward and Reverse genetics approaches. Model systems: pros and cons. Genomic editing: the CRISPR/CAS9 system. Genome-wide screens based on RNAi and CRISPR in model organisms. Functional analysis of mRNA and non-coding RNAs (ncRNA) in muscular and neuronal (mouse and human) differentiation systems. Web tools for genomics resources search and analysis (6 hours). Exercises in the computerized classroom. Elaboration and interpretation of genomic data. Biological databases (primary, secondary, specialized); the FLAT format; NCBI and resources: access via Taxonomy, Gene; Protein Map Viewer, Pubmed and Pubmed MeSH, Entrez; Genome browsers (UCSC), Ensembl, DDBJ, UniProt; Basics of gene ontology (GO). Repositories of miRBase, TargetScan and miRTARBASE.

The course of Genomics is taught in the second semester of the 3rd year of the 3-year courses in Bioinformatics and it is included among the elective courses. Basic prerequisites for understanding the topics covered by the course are a basic knowledge of Molecular Biology and Genetics. The oral and written comprehension of the English language is essential to take advantage of the oral presentations and the scientific articles proposed by the teachers as didactic material in addition to textbooks.

Textbooks at student’s choice among the followings: - R.F. Weaver Molecular Biology, Mc Graw Hill, V Edition - Watson J.D. et al Molecular Biology of the Gene, Zanichelli VII Edition - Arthur M. Lesk 2009, “INTRODUZIONE ALLA GENOMICA”, Zanichelli - Greg Gibson, Spencer V. Muse 2004, “INTRODUZIONE ALLA GENOMICA”, Zanichelli - Tom Strachan, Judith Goodship, Patrick Chinnery 2016, “GENETICA E GENOMICA”, Zanichelli Update of the texts or teaching material are distributed by the teacher on the web course page: https://elearning.uniroma1.it/course/view.php?id=4530

The course is structured in frontal theoretical lectures and computer exercises. In particular, there are 48 hours of total teaching (6 CFU). Lectures are held 3 times per week and presented by the use of slides on Power-Point. On the basis of the acquired knowledge, students will present articles already published in literature in the form of oral presentations, individually or in teams. Lessons will be delivered in Aula Psicologia II (CUO26, E01PS1L084) in blended mode. More information is available on the e-learning page of the course: https://elearning.uniroma1.it/course/view.php?id=4530

Lectures are not mandatory.

The exam aims at verifying the level of knowledge and in-depth examination of the topics of the teaching program and the reasoning skills developed by the student. The evaluation is expressed in thirtieths (minimum grade 18/30, maximum mark 30/30 with summa cum laude). The evaluation consists of an oral interview conducted by the reference teacher on the topics covered during the course. The overall exam allows verifying the achievement of the objectives in terms of knowledge and skills acquired, as well as communication skills. During the oral tests property of language, clarity of exposition and critical capacity to solve genomic problems are also evaluated. Part of the exam consists of a practical computer test to evaluate the candidate's ability to apply the skills acquired in the consultation of biological databases. The time required for the tests is 30 minutes for oral interviews and 15 minutes for the practical computer test. The final grade will result from the average between the two oral tests and the practical computer test.

Biotechnology and genomics in medicine. Sandy B. Primrose, Richard M. Twyman. Genomics: Applications in Human Biology, Chapter I. The Ever-Evolving Concept of the Gene: The Use of RNA/Protein Experimental Techniques to Understand Genome Functions. Cipriano A, Ballarino M. Front Mol Biosci. 2018 Mar 6;5:20. doi: 10.3389/fmolb.2018.00020. eCollection 2018. Review. RNA regulation: a new genetics? Mattick JS. Nat Rev Genet. 2004 Apr;5(4):316-23. Review. The relationship between non-protein-coding DNA and eukaryotic complexity. Taft RJ, Pheasant M, Mattick JS. Bioessays. 2007 Mar;29(3):288-99. Next-generation sequencing: from basic research to diagnostics. Voelkerding KV, Dames SA, Durtschi JD. Clin Chem. 2009 Apr;55(4):641-58. doi: 10.1373/clinchem.2008.112789. Epub 2009 Feb 26. Review. What is bioinformatics? A proposed definition and overview of the field. Luscombe NM, Greenbaum D, Gerstein M. Methods Inf Med. 2001;40(4):346-58. Review. A survey of best practices for RNA-seq data analysis. Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, Szcześniak MW, Gaffney DJ, Elo LL, Zhang X, Mortazavi A. Genome Biol. 2016 Jan 26;17:13. doi: 10.1186/s13059-016-0881-8. Review. Comparison of RNA-Seq and microarray in transcriptome profiling of activated T cells. Zhao S, Fung-Leung WP, Bittner A, Ngo K, Liu X. PLoS One. 2014 Jan 16;9(1):e78644. doi: 10.1371/journal.pone.0078644. eCollection 2014. Next-generation sequencing: from basic research to diagnostics. Voelkerding KV, Dames SA, Durtschi JD. Clin Chem. 2009 Apr;55(4):641-58. doi: 10.1373/clinchem.2008.112789. Epub 2009 Feb 26. Review. Library construction for next-generation sequencing: Overviews and challenges. Steven R. Head, H. Kiyomi Komori, Sarah A. LaMere, Thomas Whisenant, Filip Van Nieuwerburgh, Daniel R. Salomon, Phillip Ordoukhanian. Biotechniques. 2014; 56(2): 61–passim. doi: 10.2144/000114133 A Mouse Geneticist’s Practical Guide to CRISPR Applications. Priti Singh, John C. Schimenti, Ewelina Bolcun-Filas. Genetics. 2015 Jan; 199(1): 1–15. doi: 10.1534/genetics.114.169771 Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA. Chengzu Long, John R. McAnally, John M. Shelton, Alex A. Mireault, Rhonda Bassel-Duby, Eric N. Olson. Science. 2014 Sep 5; 345(6201): 1184–1188. doi: 10.1126/science.1254445 Yeast Two-Hybrid Screen. Lauren Makuch. Methods in Enzymology, Volume 539, Chapter III. The art and design of genetic screens: Caenorhabditis elegans. Nat Rev Genet. Jorgensen EM, Mango SE. 2002 May;3(5):356-69. Review. Drosophila, the golden bug, emerges as a tool for human genetics. Bier E. Nat Rev Genet. 2005 Jan;6(1):9-23. Review. From sequence to phenotype: reverse genetics in Drosophila melanogaster. Adams MD, Sekelsky JJ. Nat Rev Genet. 2002 Mar;3(3):189-98. Review. The art and design of genetic screens: Drosophila melanogaster. St Johnston D. Nat Rev Genet. 2002 Mar;3(3):176-88. Review. The art and design of genetic screens: mammalian culture cells. Grimm S. Nat Rev Genet. 2004 Mar;5(3):179-89. Review. The art and design of genetic screens: mouse. Kile BT, Hilton DJ. Nat Rev Genet. 2005 Jul;6(7):557-67. Review. The art and design of genetic screens: zebrafish. Patton EE, Zon LI. Nat Rev Genet. 2001 Dec;2(12):956-66. Review. Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell. 2015 Mar 12;160(6):1246-60.

The course is structured in frontal theoretical lectures and computer exercises. In particular, there are 48 hours of total teaching (6 CFU). Lectures are held 3 times per week and presented by the use of slides on Power-Point. On the basis of the acquired knowledge, students will present articles already published in literature in the form of oral presentations, individually or in teams. Lessons will be delivered in Aula Psicologia II (CUO26, E01PS1L084) in blended mode. More information is available on the e-learning page of the course: https://elearning.uniroma1.it/course/view.php?id=4530