Medical Informatics & Biostatistics Presentation

• Presentation of Prof. Dr. Andrzej Bąk
• Two email addresses: [email protected] and [email protected]
• Phone number: 32 359 11 97
• Presentation topic: Medical informatics and biostatistics
• Szkolna 9 Street, Katowice, office number 40, first floor
• "In-silico" medicine is the main topic

Topics Covered

• Data, informatics, and knowledge in medicine
• Coding of drug structure using molecular editors
• Receptors as molecular targets
• Molecular descriptors related to lipophilicity
• Computer Assisted Molecular Design (CAMD) – QSAR modeling
• Artificial intelligence (AI) essentials in medicine
• Basics of biostatistics
• Data preprocessing techniques
• Basic data modeling procedures
• Techniques for data visualization and grouping

Literature

• Recommends literature on medicinal chemistry, medical statistics, and biostatistics
• Mentions the Wold Wide Web database as a resource

Computer Assisted Drug Design (CADD)

• Aims to produce substances with desired action profiles in the human body
• Focuses on the rational production of medicines
• Involves modeling of drugs through "molecular production of properties"

Fundamentals

• Medicine: The art of human treatment and healing.
• Pharmacy/Pharmacology/Medicinal Chemistry: The science of molecules and transformations.
• Key question: What constitutes a drug molecule?
• Paracelsus (XVI century): "All things are poison, and nothing is without poison; the dose makes the poison".

History of Drug Discovery

• 5100 years ago: China used Chiang Shan herbs for fever and Ma Huang as an anti-cough drug
• Ancient Greece: Discovery of scopolamine (truth serum) and Belladonna (atropine).
• Inca nations: Used coca for energizing
• India: Development of rezorcinol (blood pressure medication)
• 1633: A Calancha monk extracted a drug from the quina tree, used to treat malaria
• 1928: Aleksander Fleming discovered penicillin (antibiotics, antybiotos)
• Penicillin discovery highlights the role of accidental findings
• Lisozyme (1921) was the first antibiotic
• Penicillin (1928) was derived from the Penicillium notatum fungus, effective against Staphylococcus
• Accident of the military health engineer named Serendepity lead to the discovery of penicilline

Regulation

• A medicinal product is any substance or mixture intended to treat or prevent disease in humans or animals, according to European Directive 2001/83/EC.
• A medicine is a substance that modifies physiological processes, inhibiting disease causes/symptoms or preventing disease development.
• Drugs are also for diagnostic purposes or modify unchanged bodily functions in Poland
• Pharmacy refers to the science of drug production and interactions with the human body
• Pharmacology studies the therapeutic application, mechanisms, and side effects of drugs
• Polish regulations are governed by pharmaceutic law, does not include "drug" term
• Permission to sell drugs in Poland is granted by the Department of Drug Registration, Medical Products and Biokilling Products

Types of Drugs

• Innovative drugs
• Generic drugs

Drug Molecules

• Remedial agents are classified according to their origin as:
  • Natural compounds: materials from plant and animal sources like vitamins, hormones, antibiotics, alkaloids etc.
  • Synthesis compounds: pure synthesis or naturally occurring compounds such as morphine, atropine, or steroids
  • Semi-synthesis compounds: a combination of synthesis and natural sources used when purely synthesized or isolated from natural source

Data Exploration in Drug Discovery

• Compares expectations and realities in new drug development
• Analyzes the number of compounds published versus the number of approved new drugs
• Considers the cost and challenges associated with drug production
• Expectations: new leading structures, many new drugs on the market
• Reality: significant experimental issues, few new drugs, and enormous cost of production

Drug Costs and Interactions

• New drugs are expensive
• Phases of drug interactions: ADMETox (Absorption, Distribution, Metabolism, Excretion, Toxicity)
• Pharmaceutical phase: involves disintegration of drug molecules and realization of the drug.
• Pharmacokinetic phase: involves the transport of drug molecules through biological barriers
• Pharmacodynamic phase: encompasses interactions of molecules with macromolecular targets

Drug Approval

• Developing takes an average of 10 years, costing over $1 billion
• This process involves multiple clinical studies (Phases I-IV), and the patent will only last for 5 years
• Discusses the reality of struggling with HIV, particularly in Africa

The Drug Discovery Cascade

• Depicts the stages of drug discovery, from initial hit identification to final drug approval
• HTS, HTS hits, Hits active, Read series, Drug candidates, Drug
• Depicts increased risk of failure

Data Analysis

• Data exploration uses experimental measures and computer simulations

Key Elements

• 150 million molecules, 1 million per year being analyzed with 800,000 publications
• Involves both deductive learning (based on calculations like QM, MM) and inductive learning (based on observation)
• Includes knowledge discovery and the significance of information in society, which will be the most valuable asset

Knowledge Discovery

• Knowledge is understanding the value of information
• Industrial society will change to an information society
• There is Storage, Sending and preceedings
• The Student has to have knowledge everywhere
• There is knowledge for the PhD level and doctor level

The Need for New Molecules

• Objective: not to make new things but enhance existing ones
• Key Aim: Molecular production of properties
• Computer science solves problems of drug design and interactions

Computer Applications

• Application of informatic methods for drug discovery, focusing on coding structures, medical databases, analysis, interactions, etc
• Defines the use of computer technology for drug design by defining the problem, biulding the models, doing calculations and analyzing data

Drug Analysis

• 2D -> 3D molecular generators (CORINA, MOPAC, BABEL, SYBYL, MOE etc.)
• Involves pre-processing descriptor selection, structure coding, and data analysis through methods

Chemoinformatics

• Highlights the integration of molecule structure, data, databases, and analysis
• Involves Chemo & bioinformatics from ligand to the target
• Drug design involves Ligand and Structure-Based Drug Discovery

Structure-based Drug Discovery

• Ligand and Structurally based approaches
• Studies CAMD with receptor ligand preparation, structural filters, docking, post-processing, and model assessment

Drug Development

• From concept to implementation: Disease definition to Metabolic toxicity. lead isolation and clinical testing

Pharmaceutics

• Directions of future evolution for finding similar items or molecules

Drug Coding

• Focuses on storing and using molecular information

Drug Presentation

• How medicine is changing with virtual models, SMILES and notations

Stereochemistry

• Racemic and stereochemistry for medicine students uses analysis and different chiral analysis
• Thalidomide is an oral medication used to treat multiple myeloma, graft-versus-host disease and skin disorders
• S is a teratogen during pregnancy
• The R gives the sedation while the S gives the toxicity

Linear Notation

• Use drug identification using notation and coding

Molecular

• Molecular surface and theory use design like Graph structure to analyze connectivity of atoms

Coding

• Drug building uses connection tables

Virtual Coding

• MDL Molfile format and Molecular editors are used as virtual tools
• SMILES is a system Molecular Input Line Entry system

SMILES System

• Simplified Molecular Input Line Entry System
• Has to be Unique and Isomeric form
• Can be absolute and canonical
• CANGEN is CANonicalization plus Generation
• Kodowanie struktury 2-etylo-1-butanolu, tertbutanolu oraz 3-propylo-4- izopropylo-1-heptenu w notacji liniowej SMILES