This document discusses proteomics and systems biology. It explains that systems biology analyzes relationships between elements in a biological system in response to genetic or environmental changes, with the goal of understanding the system. Proteomics aims to characterize proteins, including structure, function, interactions, and expression levels. Integrating omics data like genomics, proteomics and metabolomics can provide insights into biological processes and disease. Proteomics can also play roles in drug development by aiding biomarker discovery, target identification, and toxicity prediction.
Functional proteomics, methods and toolsKAUSHAL SAHU
INTRODUCTION
HISTORY
DEFINITION
PROTEOMICS
FUNCTIONAL PROTEOMICS
PROTEOMICS SOFTWARE
PROTEOMICS ANALYSIS
TOOLS FOR PROTEOM ANALYSIS
DIFFERENTS METHODS FOR STUDY OF FUNCTIONAL PROTEOMICS
APLLICATIONS
LIMITATIONS
CONCLUSION
Functional proteomics, methods and toolsKAUSHAL SAHU
INTRODUCTION
HISTORY
DEFINITION
PROTEOMICS
FUNCTIONAL PROTEOMICS
PROTEOMICS SOFTWARE
PROTEOMICS ANALYSIS
TOOLS FOR PROTEOM ANALYSIS
DIFFERENTS METHODS FOR STUDY OF FUNCTIONAL PROTEOMICS
APLLICATIONS
LIMITATIONS
CONCLUSION
With the DNA sequences of more than 90 genomes completed, as well as a draft sequence of the human genome, a major challenge in modern biology is to understand the expression, function, and regulation of the entire set of proteins encoded by an organism—the aims of the new field of proteomics. This information will be invaluable for understanding how complex biological processes occur at a molecular level, how they differ in various cell types, and how they are altered in disease states. The term proteomics describes the study and characterization of a complete set of proteins present in a cell, organ, or organism at a given time.
In general, proteomic approaches can be used (a) for proteome profiling, (b) for comparative expression analysis of two or more protein samples, (c) for the localization and identification of posttranslational modifications, and (d) for the study of protein-protein interactions. The human genome harbours 26000–31000 protein-encoding genes; whereas the total number of human protein products, including splice variants and essential posttranslational modifications (PTMs), has been estimated to be close to one million. It is evident that most of the functional information on the genes resides in the proteome, which is the sum of multiple dynamic processes that include protein phosphorylation, protein trafficking, localization, and protein-protein interactions. Moreover, the proteomes of mammalian cells, tissues, and body fluids are complex and display a wide dynamic range of proteins concentration one cell can contain between one and more than 100000 copies of a single protein.
A rapidly emerging set of key technologies is making it possible to identify large numbers of proteins in a mixture or complex, to map their interactions in a cellular context, and to analyze their biological activities. Mass spectrometry has evolved into a versatile tool for examining the simultaneous expression of more than 1000 proteins and the identification and mapping of posttranslational modifications. High-throughput methods performed in an array format have enabled large-scale projects for the characterization of protein localization, protein-protein interactions, and the biochemical analysis of protein function. Finally, the plethora of data generated in the last few years has led to approaches for the integration of diverse data sets that greatly enhance our understanding of both individual protein function and elaborate biological processes.
Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome.
Metabolomics is an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples. Combining high-throughput analytical chemistry and multivariate data analysis, metabolomics offers a window on metabolic mechanisms.
Introduction
Transcriptome analysis
Goal of functional genomics
Why we need functional genomics
Technique
1. At DNA level
2.At RNA level
3. At protein level
4. loss of function
5. functional genomic and bioinformatics
Application
Latest research and reviews
Websites of functional genomics
Conclusions
Reference
The study of the complete set of RNAs (transcriptome) encoded by the genome of a specific cell or organism at a specific time or under a specific set of conditions is called Transcriptomics.
Transcriptomics aims:
I. To catalogue all species of transcripts, including mRNAs, noncoding RNAs and small RNAs.
II. To determine the transcriptional structure of genes, in terms of their start sites, 5′ and 3′ ends, splicing patterns and other post-transcriptional modifications.
III. To quantify the changing expression levels of each transcript during development and under different conditions.
Analysis Analysis Analysis Analysisof the entire entire entire protein protein proteinproteincomplementcomplement complement complement of acell, cell, tissue, tissue, tissue, or organism organism organism under under aspecific, specific, specific, defined defined set of conditions conditions conditions .
• Relies Relies Relies on 3basic technological technological technological technological technological cornerstones cornerstones cornerstones cornerstones
• MethodMethod MethodMethod to fractionatefractionate fractionatefractionate fractionatefractionate complexcomplex complex protein/protein/ protein/ protein/ peptide peptide peptidemixturesmixtures mixtures
• MS to acquire acquire the data data necessary necessary to identify identify identifyidentifyindividual individual individual individualproteins proteins
• Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformaticsto analyze analyze and assemble assemble the MS data
With the DNA sequences of more than 90 genomes completed, as well as a draft sequence of the human genome, a major challenge in modern biology is to understand the expression, function, and regulation of the entire set of proteins encoded by an organism—the aims of the new field of proteomics. This information will be invaluable for understanding how complex biological processes occur at a molecular level, how they differ in various cell types, and how they are altered in disease states. The term proteomics describes the study and characterization of a complete set of proteins present in a cell, organ, or organism at a given time.
In general, proteomic approaches can be used (a) for proteome profiling, (b) for comparative expression analysis of two or more protein samples, (c) for the localization and identification of posttranslational modifications, and (d) for the study of protein-protein interactions. The human genome harbours 26000–31000 protein-encoding genes; whereas the total number of human protein products, including splice variants and essential posttranslational modifications (PTMs), has been estimated to be close to one million. It is evident that most of the functional information on the genes resides in the proteome, which is the sum of multiple dynamic processes that include protein phosphorylation, protein trafficking, localization, and protein-protein interactions. Moreover, the proteomes of mammalian cells, tissues, and body fluids are complex and display a wide dynamic range of proteins concentration one cell can contain between one and more than 100000 copies of a single protein.
A rapidly emerging set of key technologies is making it possible to identify large numbers of proteins in a mixture or complex, to map their interactions in a cellular context, and to analyze their biological activities. Mass spectrometry has evolved into a versatile tool for examining the simultaneous expression of more than 1000 proteins and the identification and mapping of posttranslational modifications. High-throughput methods performed in an array format have enabled large-scale projects for the characterization of protein localization, protein-protein interactions, and the biochemical analysis of protein function. Finally, the plethora of data generated in the last few years has led to approaches for the integration of diverse data sets that greatly enhance our understanding of both individual protein function and elaborate biological processes.
Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome.
Metabolomics is an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples. Combining high-throughput analytical chemistry and multivariate data analysis, metabolomics offers a window on metabolic mechanisms.
Introduction
Transcriptome analysis
Goal of functional genomics
Why we need functional genomics
Technique
1. At DNA level
2.At RNA level
3. At protein level
4. loss of function
5. functional genomic and bioinformatics
Application
Latest research and reviews
Websites of functional genomics
Conclusions
Reference
The study of the complete set of RNAs (transcriptome) encoded by the genome of a specific cell or organism at a specific time or under a specific set of conditions is called Transcriptomics.
Transcriptomics aims:
I. To catalogue all species of transcripts, including mRNAs, noncoding RNAs and small RNAs.
II. To determine the transcriptional structure of genes, in terms of their start sites, 5′ and 3′ ends, splicing patterns and other post-transcriptional modifications.
III. To quantify the changing expression levels of each transcript during development and under different conditions.
Analysis Analysis Analysis Analysisof the entire entire entire protein protein proteinproteincomplementcomplement complement complement of acell, cell, tissue, tissue, tissue, or organism organism organism under under aspecific, specific, specific, defined defined set of conditions conditions conditions .
• Relies Relies Relies on 3basic technological technological technological technological technological cornerstones cornerstones cornerstones cornerstones
• MethodMethod MethodMethod to fractionatefractionate fractionatefractionate fractionatefractionate complexcomplex complex protein/protein/ protein/ protein/ peptide peptide peptidemixturesmixtures mixtures
• MS to acquire acquire the data data necessary necessary to identify identify identifyidentifyindividual individual individual individualproteins proteins
• Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformatics Bioinformaticsto analyze analyze and assemble assemble the MS data
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
GENOMICS 5
Use these Clues+Informatiom (Leacture) to help you type your paper.
Application of Genomics in Medicine
1. What is genomics?
Genomics is the study of genes of an organism, their compositions and the interaction amongst themselves and their environment.
2. What is the application of genomics in medicine?
This is the use of genetic material from a patient for the diagnosis of a disease or to decide which therapy is most suitable. Mostly used in oncology and detection of rare infectious diseases.
3.
4. How The application of genomics in medicine would benefit the world?
Improve the screening for cancers to ensure early diagnosis. If most of the cancers can be able to be detected early enough, they can be treated. Early detection can be aided by the use of genomics.
Genomics can help diagnose some genetically linked diseases. Some diseases are passed through genes. Understanding these diseases and defects can help tame them or treat them, and look for ways to avoid their occurrence in future generations.
Through genomics, drugs can be developed against various diseases. For instance, genomics on various disease causative agents can help a lot in identifying the most suitable drug against them.
Genomics can aide the storage of bioinformatics data, which is very essential. This data can be used even in premarital counseling where the couple can be advised on whether the combination of their genes could result in any genetic conditions to their expected babies. This can help reduce the cases of genetic disorders.
· of genomics in medicine
· Oral plant vaccines; these use DNA to create surface antigens when consumed. They show potential in the immunization against Hepatitis B. The research is still underway.
· Heterologous prime-boost vaccine for malaria; Ankara virus has been used to further develop two vaccines with DNA from P. falciparum. This has shown the prospects of reducing infection rates by 80%. This is expected to e used in future.
· Anti-malarial drugs; fosmidomycin is being tested for its effect on a component involved in the life cycle of the P. falciparum parasite, which could help in the treatment of malaria.
· Screening for thalassemias; PCR has been used to observe the mutations that lead to formation of hemoglobin. This has aided in genetic counseling which has seen a significant reduction in the cases of thalassemias.
· Precision medicine; this allows the doctors to prescribe treatment based on the patient’s genetic information. This is presently being used in the medical field.
· Pharmacogenomics; this involves testing the possible outcome when a patient takes a certain medicine. Through use of genomics it is possible to identify possible side effects. This is currently being applied in the medical field.
· Genome editing; this is the deleting or adding to some portions of gene sequenc ...
Target discovery and Validation - Role of proteomicsShivanshu Bajaj
This presentation include how important is the branch proteomics in target discovery and validation for new drugs. It also include proteomic technology and current approaches in targeted proteomics
WE THE STUDENT OF PHARMACEUTICAL CHEMISTRY FROM GURUNANAK COLLEGE OF PHARMACY HAS PRESENTED QSRR, TO MAKE READERS EASILY AVAILABLE, A COMPLETE TOPIC OF MPHARM 1ST YEAR WHICH WILL MAKE THEIR STUDY AND TO COLLECT DATA MORE EASILY AT A PLACE.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. Predictive medicine involve analyzing the individual genome for
disease-susceptibilities and following pathogenic environmental
exposures by multiparameter blood analyses.
Individuals differ from one another by approximately 6 million
DNA polymorphisms, each of us will be predisposed to differing
combinations of disease. The environmental signals to which
we are all exposed will also vary greatly. Accordingly,
personalized medicine will be necessary for predicting disease.
Polymorphism refers to “a sequence variant” in some
disciplines and to “a variant found at a frequency of 1% or
higher in a population” in other disciplines.
Mutation is used to indicate both a “change” and a “disease-
causing change (frequency less than 1%)” therefore only uses
neutral terms like “variant,” “alteration,” and “change.”2
3. Systems biology
3
Systems biology is the analysis of the relationships among the
elements in a system in response to genetic or environmental
perturbations. with the goal of understanding the system or the
emergent properties of the system.
A system may be a few protein molecules carrying out a particular
task such as galactose metabolism (biomodule) , a complex set of
proteins and other molecules working together as a molecular
machine such as the ribosome, a network of proteins operating
together to carry out an important cellular function such as giving the
cell shape (protein network), or a cell or group of cells carrying out
particular phenotypic functions.
Biological system may encompass molecules, cells, organs, individuals,
or even ecosystems.
biological information moves from the genome to ecologies (DNA to
RNA to protein to biomodules or networks to cells to organs to
individuals to populations of individuals to ecologies)
4. Systems Biology in Medicine
Understand both normal biological systems and pathological
states. The ability to predict and prevent disease will always be
dictated by our fundamental knowledge of the normal and
diseased state of cells.
Treating disease will require circumventing the limitations of
specific genetic or protein defects. To do this, these defects,
which include genetic mutations, inappropriate protein
processing or folding, aberrant protein-protein or protein-DNA
interactions, and protein mislocalizations must first be
accurately placed within the context of disease.
Spawning of new technologies, which will enhance the
efficiency, scale and precision with which cellular
measurements are made. This latter influence will facilitate all
aspects of health care, including the detection and monitoring of
diseases, drug discovery, treatment evaluation, and ultimately,
predictive and preventative medicine.4
5. Proteomics and system biology
Proteins can be expressed across enormous dynamic ranges l in l06 in cells.
We do not yet know how to measure proteins across these dynamic ranges
Proteins change enormously in patterns of expression across developmental
and physiological responses.
Proteins may be altered by many environmental perturbations search
changing their information content
proteins are the actual effectors driving cell behavior, and they cannot be
studied simply by looking at the genes or mRNAs that encode them, thus
warranting the establishment of a field, now termed proteomics
Cataloguing the proteome a quantitative assessment of the full complement of
proteins within a cells the field of proteomics strives to characterize protein
structure and function, protein-protein, protein-nucleic acid, protein-lipid, and
enzyme-substrate interactions, post-translational modifications, protein
processing and folding, protein activation, cellular and sub-cellular
localization, protein turnover and synthesis rates, and even alternative
isoforms caused by differential splicing and promoter usage. In addition, the
ability to capture and compare all of this information between two cellular
states is essential for understanding cellular responses.
5
6. Proteomics and system biology
Understanding protein and gene regulatory networks of biological systems
will improve drug development efforts and eventually will lead to preventive
drugs.
Proteomics will play a major role both in developing better multiparameter
diagnostics and in the search for new therapeutic targets. Proteomics
require enormous resources to promote the development of appropriate
technologies, software and strategies. It will also play a major role in
designing preventive drugs.
Integrating different types of biological information will be critical both for
understanding biological systems and for accurately diagnosing and
monitoring disease. Computers are essential to this integration.
6
7. Proteomics and system biology
genomics, proteomics and metabonomics data were effectively
combined in a recent analysis of hydrazine liver toxicity in rats .
Acute exposure to hydrazine produces liver damage with an
accumulation of fat, causing steatosis and disturbances in the
central nervous system.
Good correlation between hepatic protein and gene expression
profiles, where 15 targets (protein/ DNA pairings) correlated to
toxic doses of hydrazine. In addition, metabolite screening,
using NMR, confirmed a disruption of lipid synthesis and
transport, which correlated with the protein and gene
expression changes associated with producing hepatic
steatosis.
7
8. PROTEOMICS IN DRUG DISCOVERY
comparative assessment of normal and diseased-state tissues,
transcription and/or expression profiling, side effect profiling,
pharmacogenomics, and the identification of biomarkers.
The majority of small molecule drugs and biologics act on protein
targets.
These proteins do not act in isolation but are embedded in cellular
pathways and networks and are thus tightly interconnected with
many other proteins and subcellular components.
Proteomics technologies have successfully been used in biomarker
discovery, target identification and validation, lead optimization, and
MOA to toxicity prediction
8
10. BIOMARKER DISCOVERY
A biomarker is a characteristic that is objectively measured and
evaluated as an indicator of normal biologic or pathogenic
processes or pharmacological responses to a therapeutic
intervention.
Biomarkers of drug efficacy and toxicity are becoming a key
need in the drug development process
Biomarkers used to diagnose disease, most are capable of
detecting the onset or advanced progression of disease, but
have little, if any, predictive power.
Increased levels of liver transaminases in blood indicates
destruction of liver cells, the prostate specific antigen (PSA) for
prostate cancer , or the troponin I and T for acute myocardial
infarction.
10
12. Toxicoproteomics
The pharmaceutical industry is focused on developing drugs with superior
safety profiles.
Toxicoproteomics utilizing global protein expression techniques to identify
key proteins and pathways in biological systems that change in response to
novel chemical entities.
An example of the use of proteomics to identify biomarkers of carcinogenicity
involved a study in which rodents were treated with the carcinogen N-
nitrosomorpholine (NNM) .
The genotoxic effect of NNM in the liver is thought to be mediated by
microsomal oxidation and results in generation of DNA adducts, induction of
DNA repair mechanisms and formation of reactive oxygen species. This
study revealed 18 differentially expressed proteins that may serve as
predictive biomarkers for the early detection of chemical-induced
carcinogenicity in rodent livers.
12