RGO5860 - Conceitos Básicos em Bioestatística (2018)

Esta disciplina tem como objetivo apresentar ao pós-graduando os conceitos básicos de bioestatística necessários para o planejamento, execução, análise e redação de um estudo científico. A disciplina é baseada na linguagem e ambiente R. É constituída por uma atividade semanal presencial onde o pós-graduando desenvolve os conceitos passo a passo de forma supervisionada e por atividades de EAD (Moodle Stoa - USP) onde estão disponíveis: aulas teóricas gravadas, textos de suporte e as atividades semanais.

Breast Cancer Genomics: Molecular Biology and High Throughput Data Analysis

1. To introduce basic knowledge on molecular biology techniques applied to mammary carcinogenesis and train researchers for storage and conservation of biological material; 2. To develop student's ability to manage breast cancer cell lines, and to understand the methods of extracting biological materials from tissues and cells in culture; 3. To introduce the basic biology of modern genomics and the experimental tools used to manipulate large-scale data generated from DNA microarray and sequencing; 4. To allow a critical evaluation of the use of molecular biology techniques as predictors of response to treatment and as prognostic factors creating perspectives for the development of targeted therapy for breast cancer;
Breast cancer is the most frequent malignant tumor affecting women worldwie (Globocan 2008). In Brazil the scenario is not different. For 2016, it is estimated that we will have 57,960 new cases of the disease in our country (Inca, 2009). According to the GLOBOCAN (International Agency for Research on Cancer) data, in 2008 691,000 new cases of breast cancer were registered in low-moderate-income countries and 692,000 in developed countries. The total number of deaths from the disease in developing countries was 268,000 compared with 189,000 deaths in developed countries. These data results in a mortality / incidence rate of 0.38 and 0.27 in low-income and high-income countries respectively (Globocan 2008 (Iarc) 2008). As death from disease is determined by treatment failure and relapse at a distance sites, the study of the molecular mechanisms involved in all stages of mammary carcinogenesis is necessary. Therefore, understanding molecular biology and its relationship with the progression of the disease is essential for training researchers in this area of knowledge.

1. Importance of prediction factors of response to therapy and prognostic factors in breast cancer. 2. Histological and molecular criteria of aggressiveness in breast cancer; 3. Control of gene expression; 4. Copy number alteration; 5. Heterogeneity and clonal evolution of breast cancer; 6. cDNA Microarray and Sequencing (DNA and RNAseq). Practices: 1. Laboratory of Molecular Biology: Methods of storage of biological material in a tumor bank; 2. Laboratory of Molecular Biology: cell culture and extraction of biological material (RNA, DNA and proteins); 3. Data analysis: a. Introduction to Linux and R; b. Public database access; c. Analysis of microarray data; d. Sequencing data analysis (DNA and RNAseq).

1. Cell and Molecular Biology: Concepts and Experiments [Hardcover] - Gerald Karp, 2009. 2. The Biology of Cancer [Hardcover] - Robert A. Weinberg, 2006. 3. Molecular Oncology of Breast Cancer [Hardcover] - Jeffrey S. Ross and Gabriel N. Hortobagyi, 2004. 4. Rosen's Breast Pathology [Hardcover] - Paul Peter Rosen, 2008. 5. The Breast: Comprehensive Management of Benign and Malignant Diseases [Hardcover] - Kirby I. Bland and Edward M. Copeland III, 2009. 6. https://www.bioconductor.org 7. https://ccb.jhu.edu/software/tophat/index.shtml 8. http://bowtie-bio.sourceforge.net/index.shtml 9. https://ccb.jhu.edu/software/hisat2/index.shtml References: 1. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GM, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA; TCGA Research Network, Perou CM. Cell. 2015 Oct 8;163(2):506-19. doi: 10.1016/j.cell.2015.09.033. 2. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S; METABRIC Group, Langerød A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Børresen-Dale AL, Brenton JD, Tavaré S, Caldas C, Aparicio S. Nature. 2012 Apr 18;486(7403):346-52. doi: 10.1038/nature10983. 3. Comprehensive molecular portraits of human breast tumours. Cancer Genome Atlas Network. Nature. 2012 Oct 4;490(7418):61-70. doi: 10.1038/nature11412. Epub 2012 Sep 23. 4. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Trapnell C1, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Nat Protoc. 2012 Mar 1;7(3):562-78. doi: 10.1038/nprot.2012.016. 5. Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016 Sep;11(9):1650-67. doi: 10.1038/nprot.2016.095.