# Biostatistics and Statistical Bioinformatics

## Presentation on theme: "Biostatistics and Statistical Bioinformatics"— Presentation transcript:

Biostatistics and Statistical Bioinformatics
Setia Pramana Universitas Brawijaya Malang, 7 October 2011

Becoming a Statistician?

Who Need Statisticians?
Can only become a lecturer/teacher? NO…… More applied fields: My classmates work in: Information and Communication Technology. Research and Developments Governments: Ministry of Finance, PLN, Bank Indonesia, Danareksa, etc. Entrepreneur Many more... Writer.... Read the book: 9 Summers 10 Autumns

Statistics Astronomy Market research Sport Economy Medical Social
Politics Biology Psychology Agriculture Industry Banking Entrepreneur

Biostatisticians

Biostatistics The study of statistics as applied to biological areas such as Biological laboratory experiments, medical research (including clinical research), and public health services research. Biostatistics, far from being an unrelated mathematical science, is a discipline essential to modern medicine – a pillar in its edifice’ (Journal of the American Medical Association (1966)

Biostatistics Public Health: Epidemiology
Modeling Infectious Diseases: HIV, HCV Disease Mapping Genetics: family related disease Bioinformatics Image Processing Data Mining Pattern recognition etc

Biostatistics Agriculture Experimental Design Genetics
Biomedical Research Evidence-based medicine Clinical studies Drug Development

Statistical Methods? t-test ANOVA Regression Cluster analysis
Discriminant analysis Non-Linear Modeling Multiple comparison Linear Mixed Model Bayesian Etc, z

Biostatisticians in Drug development

Drugs Development Takes 10-15 years Cost more than 1 million USD
To ensure that only the drugs that are that are both safe and effective can be marketed. Stages: - Drug Discovery - Pre-clinical Development - Clinical Development -> 4 Phases Statisticians are involved in all stages (a must)

Pharmaceutical development
discovery of compound; synthesis and purification of drug substance; manufacturing procedures Pharmaceutical development Pre-clinical (animal) studies pharmacological profile; acute toxicity; effects of long-term usage Investigational New Drug application Phase I clinical trials small; focus on safety medium size; focus on safety and short-term efficacy; Phase II clinical trials Phase III clinical trials large and comparative; focus on efficacy and cost benefits New Drug Application „real world” experience; demonstrate cost benefits; rare adverse reactions Phase IV clinical trials 12

International Conference on Harmonization (ICH)
The international harmonization of requirements for drug research and development so that information generated in one country or area would be acceptable to other countries or areas. Regions: Europe, USA, Japan. All clinical trials must follow ICH regulations. Statistics plays important role. Statistical Principles for Clinical Trials (ICH E9).

Preclinical and Clinical Development
Statisticians are involved from the beginning of the study Planning the study Formulating the hypothesis Choosing the endpoint Choosing the design and sample size Conduct of the study Patient accrual Data collection Data Quality control, Data analysis Publication of results

bioinformatics

Bioinformatics Bioinformatics is a science straddling the domains of biomedical, informatics, mathematics and statistics. Applying computational techniques to biology data Functional Genomics Proteomics Sequence Analysis Phylogenetic Etc,.

“Informatics” in Bioinformatics
Databases Building, Querying Object DB •Text String Comparison Text Search Finding Patterns AI / Machine Learning Clustering Data mining etc

Central Dogma of Molecular Biology
Genes contain construction information All structure and function is made up by proteins

Genomics Premise: Physiological changes -> Gene expression changes -> mRNA abundance level changes Objective: Use gene expression levels measured via DNA microarrays to identify a set of genes that are differentially expressed across two sets of samples (e.g., in diseased cells compared to normal cells)

Microarrays Technology
DNA microarrays are a new and promising biotechnology which allow the monitoring of expression of thousand genes simultaneously

Gene Expression Analysis
Overview of the process of generating high throughput gene expression data using microarrays.

Preprocessed data Genes C1 C2 C3 T1 T2 T3

Applications High efficacy and low/no side effect drug
Personalized medicine. Genes related disease. Biological discovery new and better molecular diagnostics new molecular targets for therapy finding and refining biological pathways Molecular diagnosis of leukemia, breast cancer, Appropriate treatment for genetic signature Potential new drug targets

Challenges Mega data, difficult to visualize
Too few records (columns/samples), usually < 100 Too many rows(genes), usually > 1,000 Too many columns likely to lead to False positives for exploration, a large set of all relevant genes is desired for diagnostics or identification of therapeutic targets, the smallest set of genes is needed model needs to be explainable to biologists

Microarray Data Analysis Types
Gene Selection find genes for therapeutic targets Classification (Supervised) identify disease (biomarker study) predict outcome / select best treatment Clustering (Unsupervised) find new biological classes / refine existing ones Understanding regulatory relationship/pathway exploration

Gene Selection Modified t-test
Significance Analysis of Microarray (SAM) Limma (Linear model for microarrays ) Random forest Lasso (least absolute selection and shrinkage operator) Linear Mixed model Elastic-net Etc,

Visualization Dimensionality reduction
PCA (Principal Component Analysis) Biplot Multi dimensional scaling Etc

Clustering Cluster the genes Cluster the arrays/conditions
Cluster both simultaneously K-means Hierarchical Biclustering algorithms

Clustering Cluster or Classify genes according to tumors
Cluster tumors according to genes

Biclustering A biclustering method is an unsupervised learning method which looks for sub-matrices in a data matrix with a high similarity of elements. Algorithms: Statistical based, AI, machine learning. BiclustGUI: A User Friendly Interface for Biclustering Analysis

Bicluster Structure

Software/Statistical Packages
Minitab SAS SPSS R S-Plus Matlab Stata

R now is growing, especially in bioinformatics
Statistics, data analysis, machine learning Free High Quality Open Source Extendable (you can submit and publish your own package!!) Can be integrated with other languages (C/C++, Java, Python) Large active user community Command-based (-)

Summary Statisticians can flexibly get involved in many fields.
Only tools, applications are widely range. Biostatisticians have many opportunities in public health services ( Centers for Disease Control and Prevention, CDC), pharmaceutical companies, research institutions etc. Statistical Bioinformatics: cutting edge technology -> methods are growing -> many more developments in future.