3Who Need Statisticians? Can only become a lecturer/teacher?NO…… More applied fields:My classmates work in:Information and Communication Technology.Research and DevelopmentsGovernments: Ministry of Finance, PLN, Bank Indonesia, Danareksa, etc.EntrepreneurMany more...Writer....Read the book: 9 Summers 10 Autumns
4Statistics Astronomy Market research Sport Economy Medical Social PoliticsBiologyPsychologyAgricultureIndustryBankingEntrepreneur
6BiostatisticsThe 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)
7Biostatistics Public Health: Epidemiology Modeling Infectious Diseases: HIV, HCVDisease MappingGenetics: family related diseaseBioinformaticsImage ProcessingData MiningPattern recognitionetc
8Biostatistics Agriculture Experimental Design Genetics Biomedical ResearchEvidence-based medicineClinical studiesDrug Development
11Drugs 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 PhasesStatisticians are involved in all stages (a must)
12Pharmaceutical development discovery of compound; synthesisand purification of drug substance; manufacturing proceduresPharmaceutical developmentPre-clinical (animal) studiespharmacological profile; acute toxicity; effects of long-term usageInvestigational New Drug applicationPhase I clinical trialssmall; focus on safetymedium size; focus on safety and short-term efficacy;Phase II clinical trialsPhase III clinical trialslarge and comparative; focus on efficacy and cost benefitsNew Drug Application„real world” experience; demonstrate cost benefits; rare adverse reactionsPhase IV clinical trials12
13International 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).
14Preclinical and Clinical Development Statisticians are involved from the beginning of the studyPlanning the studyFormulating the hypothesisChoosing the endpointChoosing the design and sample sizeConduct of the studyPatient accrualData collectionData Quality control, Data analysisPublication of results
16BioinformaticsBioinformatics is a science straddling the domains of biomedical, informatics, mathematics and statistics.Applying computational techniques to biology dataFunctional GenomicsProteomicsSequence AnalysisPhylogeneticEtc,.
18Central Dogma of Molecular Biology Genes contain construction informationAll structure and function is made up by proteins
19GenomicsPremise: Physiological changes -> Gene expression changes -> mRNA abundance level changesObjective: 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)
20Microarrays Technology DNA microarrays are a new and promising biotechnology which allow the monitoring of expression of thousand genes simultaneously
21Gene Expression Analysis Overview of the process of generating high throughput gene expression data using microarrays.
23Applications High efficacy and low/no side effect drug Personalized medicine.Genes related disease.Biological discoverynew and better molecular diagnosticsnew molecular targets for therapyfinding and refining biological pathwaysMolecular diagnosis of leukemia, breast cancer,Appropriate treatment for genetic signaturePotential new drug targets
24Challenges Mega data, difficult to visualize Too few records (columns/samples), usually < 100Too many rows(genes), usually > 1,000Too many columns likely to lead to False positivesfor exploration, a large set of all relevant genes is desiredfor diagnostics or identification of therapeutic targets, the smallest set of genes is neededmodel needs to be explainable to biologists
25Microarray Data Analysis Types Gene Selectionfind genes for therapeutic targetsClassification (Supervised)identify disease (biomarker study)predict outcome / select best treatmentClustering (Unsupervised)find new biological classes / refine existing onesUnderstanding regulatory relationship/pathwayexploration
26Gene Selection Modified t-test Significance Analysis of Microarray (SAM)Limma (Linear model for microarrays )Random forestLasso (least absolute selection and shrinkage operator)Linear Mixed modelElastic-netEtc,
28Clustering Cluster the genes Cluster the arrays/conditions Cluster both simultaneouslyK-meansHierarchicalBiclustering algorithms
29Clustering Cluster or Classify genes according to tumors Cluster tumors according to genes
30BiclusteringA 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
33R now is growing, especially in bioinformatics Statistics, data analysis, machine learningFreeHigh QualityOpen SourceExtendable (you can submit and publish your own package!!)Can be integrated with other languages (C/C++, Java, Python)Large active user communityCommand-based (-)
34Summary 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.