December 14, 2009

Applications of Systems Biology in Drug Discovery

Filed under: Bioinformatics,Chemoinformatics,Systems Biology — Biointelligence: Education,Training & Consultancy Services @ 4:33 am
Tags: , , ,

Till date we have made a lot of posts on Systems Biology, its applications and it scope. Indeed, Systems Biology has brought a big revolution in cell biology and pathway analysis. When seen in combination with treatment of diseases and drug discovery, it proves even more handy. Here we discuss Systems Biology in combination with drug discovery.

The goal of modern systems biology is to understand physiology and disease from the level of molecular pathways, regulatory networks, cells, tissues, organs and ultimately the whole organism. As currently employed, the term ‘systems biology’ encompasses many different approaches and models for probing and understanding biological complexity, and studies of many organisms from bacteria to man. Much of the academic focus is on developing fundamental computational and informatics tools required to integrate large amounts of reductionist data (global gene expression, proteomic and metabolomic data) into models of regulatory networks and cell behavior. Because biological complexity is an exponential function of the number of system components and the interactions between them, and escalates at each additional level of organization.

There are basically three advances in the practical applications of systems biology to drug discovery. These are:

1. Informatic integration of ‘omics’ data sets (a bottom-up approach)

Omics approaches to systems biology focus on the building blocks of complex systems (genes, proteins and metabolites). These approaches have been adopted wholeheartedly by the drug industry to complement traditional approaches to target identification and validation, for generating hypotheses and for experimental analysis in traditional hypothesis-based methods.

2. Computer modeling of disease or organ system physiology from cell and organ response level information available in the literature (a top-down approach to target selection, clinical indication and clinical trial design).
The goal of modeling in systems biology is to provide a framework for hypothesis generation and prediction based on in silico simulation of human disease biology across the multiple distance and time scales of an organism. More detailed understanding of the systems behavior of intercellular signaling pathways, such as the identification of key nodes or regulatory points in networks or better understanding of crosstalk between pathways, can also help predict drug target effects and their translation to organ and organism level physiology.

3.  The use of complex human cell systems themselves to interpret and predict the biological activities of drugs and gene targets (a direct experimental approach to cataloguing complex disease-relevant biological responses).

Pathway modeling as yet remains too disconnected from systemic disease biology to have a significant impact on drug discovery. Top-down modeling at the cell-to-organ and organism scale shows promise, but is extremely dependent on contextual cell response data. Moreover, to bridge the gap between omics and modeling, we need to collect a different type of cell biology data—data that incorporate the complexity and emergent properties of cell regulatory systems and yet ideally are reproducible and amenable to storing in databases, sharing and quantitative analysis.

This is how Systems Biology has aided in Drug Discovery Research and paved its path to cure many vital diseases.

Read our other posts on Systems Biology –

November 17, 2009

OrChem: A Chemistry Search Engine for Oracle

Filed under: Bioinformatics,Chemoinformatics — Biointelligence: Education,Training & Consultancy Services @ 10:46 am
Tags: , , ,

Registration, indexing and searching of chemical structures in relational databases is one of the core areas of cheminformatics. Research on the topic goes back to the 1960s and probably before that. However, little detail has been published on the inner workings of search engines and developments have been mostly closed-source. This has led to the situation that despite more than thirty years of research and publications very few open reference code is available for use and study. The cheminformatics open source community has been working since the mid 1990s to overcome this problematic situation.

OrChem, an extension for the Oracle 11G database that adds registration and indexing of chemical structures to support fast substructure and similarity searching. The cheminformatics functionality is provided by the Chemistry Development Kit. OrChem provides similarity searching with response times in the order of seconds for databases with millions of compounds, depending on a given similarity cut-off. For substructure searching, it can make use of multiple processor cores on today’s powerful database servers to provide fast response times in equally large data sets.

OrChem is built on top of the Chemistry Development Kit (CDK) and depends on this Java library in numerous ways. For example, compounds are represented internally as CDK molecule objects, the CDK’s I/O package is used to retrieve compound data, and its subgraph isomorphism algorithms are used for substructure validation. OrChem adds its own Java layer on top of the CDK to implement fast database storage and retrieval. With the CDK loaded into Oracle, a large cheminformatics library becomes readily available to PL/SQL. With little effort developers can build database functions around the CDK and so quickly implement chemistry extensions for Oracle. OrChem works in the same way, using the CDK where possible.

It uses chemical fingerprints to find compounds by substructure or similarity criteria. Fingerprints are bitsets in which each bit indicates the presence or absence of a particular chemical aspect. During a similarity search the fingerprints are used to calculate a Tanimoto measure. A Tanimoto similarity measure between two binary fingerprints is defined by the ratio of the number of common bits set to one to the total number of bits set to one in the two fingerprints. For substructure searching the fingerprint has a different function: it is used to screen possible candidates before a computationally more expensive isomorphism test.

The Orchem search engine would definately prove benefical to the cheminformatics community. More can be read on Orchem here:

September 18, 2009

Chemoinformatics Companies Worldwide

Here is a list of companies working in Chemoinformatics and Drug Discovery.

Also check out these:

August 11, 2009

Bioinformatics In Pharma Industry

Bioinformatics provides the computational support for functional genomics which will link the behavior of cells, organism amd population to the information encoded in the genomes, as well as structural genomics. The utility of bioinformatics lies in the identification of useful genes leading to the development of new gene products. The subject covers topics such as protein modeling and sequence alignment, expression data analysis, and comparartive genomics. It combines algorithmic, statistical and database methods for studying biological problems also.

The greatest achievement of bioinformatics methods, the Human Genome Project. Because of this the nature and priorities of bioinformatics research and applications are changing. Many experts believe that this will affect bioinformatics in several ways. For instance some scientists also believe what some people refer to as research or medical informatics, the management of all biomedical experimental data associated with particular molecules or patients – from mass spectroscopy, to in vitro assays to clinical side-effects-move from the concern of those working in drug company and hospital IT (information technology) into the mainstream of cell and molecular biology and migrate from the commercial and clinical to academic sectors.

Drug Development

Only 10% of drug molecules identified in research make it through development. This means that many potential drugs do not make it to market, and expensive time and resources are invested m molecules that will generate no revenue. Simulation and informatics can significantly increase these odds by improving the efficiency of drug development, cutting costs, and improving margins.

Formulation Design

Formulation is the process of mixing Ingredients in such a way as to produce a new or improved product. The formulation department must balance the different marketing and deliverability requirements with cost and chemical constraints to come up with the best possible drug delivery method at the best price. With laboratory results stored in legacy systems, it takes expert company knowledge and experience to know which methods and suppliers are available, let alone to locate them quickly. In many cases scientists find that it is easier to repeat an experiment than to find previous results. This situation is compounded in global R&D set-ups, and after mergers and acquisitions.

Crystallisation and Structure Determination

Determining the crystal structure of an active compound is one of the first steps in pharmaceutical development. The crystal structure of a drug affects how easy it is to formulate, its bio-avail- ability, and its shelf life. Knowledge of the different possible polymorphs of a crystal can also give better patent protection for a drug.

Polymer Modeling

Drug delivery is a complex task. The drug must be delivered in a way that transports the active component intact to the appropriate part of the body. The way the cell takes up the drug is also very important: drugs that go to parts of the body other than the intended target are wasted and may lead to unwanted side effects.

Many delivery devices are polymeric with the drug either solubilised or emulsified in the polymer. Drug delivery systems have mesoscale structures; between 10 to 1000 nm. The amount of computing power required to model these systems at an atomistic level is prohibitive, and macroscale techniques such as Finite element analysis or computational fluid dynamics do not give the required level of detail. Mesoscale modeling, focusing on the nanometer length scale, is helping scientists to develop colloidal delivery systems for drugs.

The great advances in human healthcare that are presaged by the Human Genome Project can be realized by the pharmaceutical industry. A prerequisite for this will be the successful integration of bioinformatics into most aspects of drug discovery. Although, from a scientific viewpoint, this is not a difficult problem, there are formidable technological obstacles. Once these are overcome, rapid progress can be expected.

August 4, 2009

Education in Chemoinformatics

Filed under: Chemoinformatics — Biointelligence: Education,Training & Consultancy Services @ 2:47 am
Tags: , , , ,
Chemoinformatics is rapidly becoming a core part of drug design informatics, yet the educational
opportunities in the field are currently limited.Like many of today’s emerging life science fields, chemoinformatics
has become a ‘hot topic’ while it is still in the process of
finding its identity. Indeed it is not yet clear how to spell the name
of the field: some prefer cheminformatics – no ‘o’ – and others,
including ourselves, use entirely different terms, such as chemical
informatics. What is clear is that the techniques that this field
concerns itself with – the processing of chemical and related
information on computers – are becoming central to the processes
of modern drug discovery.Here

Here is a small post which gives an overview of the current requirements and the courses available in Cheminformatics.

Chemoinformatics is rapidly becoming a core part of drug design informatics, yet the educational opportunities in the field are currently limited.

Like many of today’s emerging life science fields, chemoinformatics has become a ‘hot topic’ while it is still in the process of finding its identity.

Indeed it is not yet clear how to spell the name of the field: some prefer cheminformatics – no ‘o’ – and others, including ourselves, use entirely different terms, such as chemical informatics. What is clear is that the techniques that this field concerns itself with – the processing of chemical and related information on computers – are becoming central to the processes of modern drug discovery.

Interest in chemoinformatics is now becoming widespread, but this greatly increased exposure has highlighted the fact that there are very few people with high-level chemoinformatics skills. The principal source of such individuals in the past has been doctoral students and post-doctoral staff who have spent time in one of the few academic groups world-wide who carry out research in this area, with job opportunities also becoming available to individuals who have worked in areas of chemistry that involve significant computation – such as X-ray crystallography or computational chemistry – or in related areas such as bioinformatics or computational biology. However, there are still too few trained staff available to meet the emerging need, and this has spurred the development of university courses that can provide students with the necessary skills, at both undergraduate and postgraduate levels.

Academic Programs in Chemoinformatics

A small number of universities have established chemoinformatics programs . The most widely recognized and well-established research and teaching base in the field is the Department of Information Studies at the University of Sheffield, which offers Master of science (MSc, or MS) degree and PhD qualifications in chemoinformatics. Subsequent programs have been developed at the University of Manchester Institute of Science and Technology (UMIST), now merged with the University of Manchester, UK, and the School of Informatics at Indiana University (IU), IN, USA.

For a more detailed view refer to the following links:

August 3, 2009

Careers and Opportunities in Chemoinformatics

Filed under: Bioinformatics,Chemoinformatics — Biointelligence: Education,Training & Consultancy Services @ 2:56 am
Tags: , , , ,

After Bioinformatics the next new buzz is Chemoinformatics.. but what is it. Here is an article which I found.

When two scientific disciplines meet, they can be mutually beneficial, fill each other’s voids – and complement each other, giving rise to unprecedented scientific opportunities. One such field of recent interest is chemoinformatics. Chemoinformatics plays a key role in areas as diverse as chemical genomics and drug discovery, the storage of chemical information in databases and the prediction of toxic substances. Today, these techniques are mostly used in pharmaceutical companies in the process of drug discovery, but also for example in “functional foods”, designed by nutritional companies to improve body functions, such as for example digestion or brain function.

While bioinformatics is known since 1976 which is defined as “the study of informatics process in biotic systems”, the emerging terminology in the pharmaceutical sector is commonly referred to as chemoinformatics, which is defined as the “mixing of information resources to transform data into information and information into knowledge, intending for better rapid decisions in the arena of drug lead identification and optimization”.

Chemoinformatics is a generic term that encompasses the design, creation, organization, storage, management, retrieval, analysis, dissemination, visualization and the use of chemical information – so, virtually every area where “chemical data” is accessed or changed by means of computers. Chemoinformatics represents a vital link between experiment and theory in the area of drug design, through the extraction of information from data and conversion into knowledge. With the explosion of publicly available genomic information, such as that resulting from the Human Genome Project, in the middle of the 1990s, bioinformatics has become very popular not only in the scientific community but also among the general audience. This has led to the coining of the counterpart of bioinformatics in chemistry after about two decades as Chemoinformatics. However this field can actually be seen as about two hundred years old – ever since the first account of chemical data has been published in literature.

Today’s technology in chemoinformatics in fact facilitates better organization, storage, retrieval and analysis of these data for further advanced predicting studies – thus, saving time and money, also possibly animal experiments, and advancing humankind by developing novel, and safer, drugs. The last three decades have seen tremendous growth in this field with the advancement in the computer technologies. Today volumes and volumes of books has been written on this subject and even few text books available for teaching in universities at the BSc and MSc level. Though there are full time Masters degree programs available in universities abroad, in India this field has yet to get full recognition.

Currently chemoinformatics is being introduced as part of an ongoing diploma or masters program in bioinformatics in spite of its maturity as a new discipline. Besides the traditional mainstream areas of chemoinformatics such as database systems, computer-assisted structure elucidation systems, computer-assisted synthesis design systems, and quantitative structure-activity relationship (QSAR), several new research areas of chemoinformatics have appeared recently, such as in silico library design, virtual screening, docking, prediction of ADME (Absorption, distribution, metabolism and excretion) and toxicity. It is interesting to notice that at the end of 20th century almost all the major foundations and theories of chemistry had been well understood and established. Chemistry has already evolved from largely a study of the elements to a study of molecules to currently a study of molecular interactions, especially those involving biological macromolecules – the molecules such as proteins and sugars we humans are made of.

This offers a excellent opportunity for chemoinformatics to grow in this new direction. The main focus of recently identified “cyber enabled chemistry” by the US National Science Foundation is on the development of integrated databases, data mining tools, molecular visualization and computational capabilities and the remote and networked use of instrumentation. The scope of this rapidly developing field will certainly continue to expand. It is worth mentioning that there is a new trend of integration of chemoinformatics with bioinformatics. This is because many sectors of the chemical and pharmaceutical industries are interdisciplinary by nature, and major progress and developments in those industries are occurring in both bioinformatics and chemoinformatics side by side. Chemists will become more and more computer dependent, Internet dependent and chemoinformatics dependent. Chemoinformatics through its development in the past half a century, has reached in the present wide acceptance, and will have a bright future!

The purpose of this particular article is to highlight the various research and job opportunities available to a new generation of students in chemistry, computer science and biology at various levels in both academic and pharmaceutical environment.

Job Title of Recent Graduates

Graduates from the MSc in Chemoinformatics have taken up a variety of different types of posts upon starting employment. Examples of the job titles of recent graduates are given below: Chemoinformatics Scientist, Computational Chemist, Chemical Data Scientist, Regulatory Affairs Officer, Senior Information Analyst, Information Officer, Data Officer, Graduate IT Trainee, Programmer, QSAR Software Tester, Support Analyst, Business Analyst, Technical Editor, Consultant, Research Assistant  Organizations/Companies of Recent Graduates etc.,

Graduates from the MSc in Chemoinformatics obtain posts with a wide range of organizations and companies. Some of the companies sponsoring chemoinformatics products and activities include: Abbott Laboratories, AstraZeneca, Advanced Chemistry Development, Accelrys, Chemical Computing Group, Barnard Chemical Information Ltd., Beilstein, Jubilant Biosys, Johnson & Johnson, Lilly, Lupin, General Electrics, GlaxoSmithKline, Hoffman La Roche, Novartis, Molecular Design Limited, Merck, Pfizer, Proctor and Gamble, Ranbaxy, Tripos, Unilever, Wyeth etc.,

Some of the research laboratories / Universities / Not for profit organizations actively involved in chemoinformatics activities include: National Chemical Laboratory-Pune, CDRI-Lucknow, RRL-Jammu, Indian Institute of Technology (Delhi), Indian Institute of Science, University of Leeds (UK), Royal Society of Chemistry, University of Sheffield (UK), University of Erlangen (Germany), University of North Carolina (USA), Pune University (India), Chemical Abstract Service (American Chemical Society, USA) etc.