Assignent-01/Abhishek Mishra/HBTI Kanpur Bioinformatics-Programs & Tools:

Bioinformatics tools are software programs that are designed for extracting the meaningful information from the mass of data & to carry out this analysis step. Factors that must be taken into consideration when designing these tools are The end user (the biologist) may not be a frequent user of computer technology These software tools must be made available over the internet given the global distribution of the scientific research community Major categories of Bioinformatics Tools: There are both standard and customized products to meet the requirements of particular projects. There are data-mining software that retrieves data from genomic sequence databases and also visualization tools to analyze and retrieve information from proteomic databases. These can be classified as homology and similarity tools, protein functional analysis tools, sequence analysis tools and miscellaneous tools. Here is a brief description of these. Everyday bioinformatics is done with sequence search programs like BLAST, sequence analysis programs, like the EMBOSS and Staden packages, structure prediction programs like THREADER or PHD or molecular imaging/modeling programs like RasMol and WHATIF. Homology and Similarity Tools: Homologous sequences are sequences that are related by divergence from a common ancestor. Thus the degree of similarity between two sequences can be measured while their homology is a case of being either true or false. This set of tools can be used to identify similarities between novel query sequences of unknown structure and function and database sequences whose structure and function have been elucidated. Protein Function Analysis: These groups of programs allow you to compare your protein sequence to the secondary (or derived) protein databases that contain information on motifs, signatures and protein domains. Highly significant hits against these different pattern databases allow you to approximate the biochemical function of your query protein. Structural Analysis: These sets of tools allow you to compare structures with the known structure databases. The function of a protein is more directly a consequence of its structure rather than its sequence

Applications and software Tools for Bioinformatics

Assignent-01/Abhishek Mishra/HBTI Kanpur

with structural homologs tending to share functions. The determination of a protein's 2D/3D structure is crucial in the study of its function.

Sequence Analysis: This set of tools allows you to carry out further, more detailed analysis on your query sequence including evolutionary analysis, identification of mutations, hydropathy regions, CpG islands and compositional biases. The identification of these and other biological properties are all clues that aid the search to elucidate the specific function of your sequence.

NCBI-BLAST: (National Centre of Biotechnology Information-Basic Local Alignment Search Tool)

BLAST is used to finds region of local similarity between sequences. The program compares the nucleotide or protein sequences to sequence database and calculate the statistical significance of matches. BLAST can be used to infer functional and evolutionary relationship between sequences as well as help identify members of gene families. BLAST comes under the category of homology and similarity tools. It is a set of search programs designed for the Windows platform and is used to perform fast similarity searches regardless of whether the query is for protein or DNA. Comparison of nucleotide sequences in a database can be performed. Also a protein database can be searched to find a match against the queried protein sequence. NCBI has also introduced the new queuing system to BLAST (Q BLAST) that allows users to retrieve results at their convenience and format their results multiple times with different formatting options. Depending on the type of sequences to compare, there are different programs: Blastp compares an amino acid query sequence against a protein sequence database Blastn compares a nucleotide query sequence against a nucleotide sequence database Blastx compares a nucleotide query sequence translated in all reading frames against a protein sequence database tblastn compares a protein query sequence against a nucleotide sequence database dynamically translated in all reading frames tblastx compares the six-frame translations of a nucleotide query sequence against the sixframe translations of a nucleotide sequence database.

FASTA:
FAST homology search all sequences .An alignment program for protein sequences created by Pearsin and Lipman in 1988. The program is one of the many heuristic algorithms proposed to speed up sequence comparison. The basic idea is to add a fast prescreen step to locate the highly matching segments between two sequences, and then

Applications and software Tools for Bioinformatics

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extend these matching segments to local alignments using more rigorous algorithms such as Smith-Waterman.

ClustalW:
It is a fully automated sequence alignment tool for DNA and protein sequences. It returns the best match over a total length of input sequences, be it a protein or a nucleic acid.

RasMol:
It is a powerful research tool to display the structure of DNA, proteins, and smaller molecules. Protein Explorer, a derivative of RasMol, is an easier to use program.

PROSPECT: (PROtein Structure Prediction and Evaluation Computer ToolKit)

PROSPECT is a protein- structure prediction system that employs a computational technique called protein threading to construct a protein's 3-D model.

PatternHunter:
PatternHunter, based on Java, can identify all approximate repeats in a complete genome in a short time using little memory on a desktop computer. Its features are its advanced patented algorithm and data structures, and the java language used to create it. The Java language version of PatternHunter is just 40 KB, only 1% the size of Blast, while offering a large portion of its functionality.
Applications and software Tools for Bioinformatics

COPIA: (COnsensus Pattern Identification and Analysis)

COPIA is a protein structure analysis tool for discovering motifs (conserved regions) in a family of protein sequences. Such motifs can be then used to determine membership to the family for new protein sequences, predict secondary and tertiary structure and function of proteins and study evolution history of the sequences.

AutoDock:
AutoDock is a suite of automated docking tools. It is design to predict how small molecule, such as substrate or drug candidates, bind to a receptor of known 3D structure.

AutoDock Vina:
AutoDock Vina is a new open source program for drug discovery, molecular docking & virtual screening, offering multi core capability, high performance and enhanced accuracy and ease of use.

EMBOSS: (European Molecular Biology Open Software Suite)

EMBOSS is a new, free open source software analysis package specially developed for the need of molecular biology user community. The software automatically copes with data in a variety of formats and even allows transparent retrieval of sequence data from the web. Also,

Assignent-01/Abhishek Mishra/HBTI Kanpur

as extensive libraries are provided with package, it is a platform to allow other scientist to developed and release software in true open source spirit. EMBOSS also integrates a range of currently available packages and tool for sequence analysis into a seamless whole.

ClustalX:
ClastalX is a window interfaces for ClastalW multiple sequence alignment programs. It provides an integrated environment for performing multiple sequence and profile alignments and analyzing the results. The sequence alignment is displayed in a window on the screen. A versatile coloring scheme has been incorporated allowing you to highlight conserve features in the alignment. The pool-down means at the top of window allow to you select all the position required for traditional multiple sequence and profile alignment.

MODELLER:
MODELLER is used for homology or comparative modeling of protein three dimensional structures. The user provides an alignment of a sequence to be modeled with known related structures and MODELLER automatically calculates a mode containing all non-hydrogen atoms. MODELLER implements comparative protein structure modeling by satisfaction of spatial restraints and can perform many additional task, including de novo modeling of loop in protein structure, optimization of various models of protein structure with respect to flexibly defined objective function, multiple alignment of protein sequence and/or structures, clustering, searching of sequence database, comparison of protein structure etc.
Applications and software Tools for Bioinformatics

Glimmer:
Glimmer is a system for finding genes in microbial DNA, especially the genomes of bacteria, archaea and virus. Glimmer (Gene Locator and interpolated Markov ModelER) uses interpolated Markov models (IMMs) to identify the coding regions and distinguish them from noncoding DNA. .

Chemtool:
Chemtool is a program for drawing organic molecules easily and store them in a variety of output formats including as an X bitmap, Xfig, SVG or EPS file. It runs under the X window system using the GTK widget set.

Avogadro:
An advanced molecular editor designed for cross platform use in computational chemistry, molecular modeling, bioinformatics, material science, and related areas, which offers flexible rendering and a powerful plugin architecture.

GROMACS:
It is a versatile and extremely well optimized package to perform molecular dynamics computer simulation and subsequent trajectory analysis. It is developed for biomolecule like

Assignent-01/Abhishek Mishra/HBTI Kanpur

protein, but the extremely high performance means it is also used also in several other fields like polymer chemistry and solid state physics.

Jackal:
Jackal is a collection of program designed for modeling and analysis of program structure. Its core program is a versatile homology modeling package nest.

HMMER:
Profile hidden Markov models (Profile HMMs) can be used to do sensitive database searching using statistical description of a sequence familys consensus. HMMER is a freely distributable implementation of profile HMM software for protein sequence analysis.

NCBI Genome Workbench:

NCBI Genome Workbench is an integrated application for viewing and analyzing sequence data. With Genome Workbench, we can view data in publically available sequence database at NCBI, and mix this data with your own private data. Genomes Workbench can display sequence data in many ways, including graphical sequence views, various alignment views, phylogenetic tree views, and tabular views of data. It can also align your private data to data in public data, and retrieve BLAST results.

Bioinformatics Projects
BioJava
Applications and software Tools for Bioinformatics

The BioJava Project is dedicated to providing Java tools for processing biological data which includes objects for manipulating sequences, dynamic programming, file parsers, simple statistical routines, etc. BioPerl The BioPerl project is an international association of developers of Perl tools for bioinformatics and provides an online resource for modules, scripts and web links for developers of Perl-based software.

BioXML
A part of the BioPerl project, this is a resource to gather XML documentation, DTDs and XML aware tools for biology in one location.

Biocorba
Interface objects have facilitated interoperability between bioperl and other perl packages such as Ensembl and the Annotation Workbench. However, interoperability between bioperl and packages written in other languages requires additional support software. CORBA is one such framework for interlanguage support, and the biocorba project is currently implementing a CORBA interface for bioperl. With biocorba, objects written within bioperl will be able to communicate with objects written in bio python and biojava.

Assignent-01/Abhishek Mishra/HBTI Kanpur

Bioinformatics Applications
Molecular medicine: The human genome will have profound effects on the fields of biomedical research and clinical medicine. Every disease has a genetic component. This may be inherited (as is the case with an estimated 3000-4000 hereditary disease including Cystic Fibrosis and Huntingtons disease) or a result of the body's response to an environmental stress which causes alterations in the genome (e.g. cancers, heart disease, diabetes.). The completion of the human genome means that we can search for the genes directly associated with different diseases and begin to understand the molecular basis of these diseases more clearly. This new knowledge of the molecular mechanisms of disease will enable better treatments, cures and even preventative tests to be developed. Personalised medicine: Clinical medicine will become more personalized with the development of the field of pharmacogenomics. This is the study of how an individual's genetic inheritance affects the body's response to drugs. At present, some drugs fail to make it to the market because a small percentage of the clinical patient population shows adverse effects to a drug due to sequence variants in their DNA. As a result, potentially lifesaving drugs never makes it to the marketplace. Today, doctors have to use trial and error to find the best drug to treat a particular patient as those with the same clinical symptoms can show a wide range of responses to the same treatment. In the future, doctors will be able to analyses a patient's genetic profile and prescribe the best available drug therapy and dosage from the beginning. Preventative medicine: With the specific details of the genetic mechanisms of diseases being unraveled, the development of diagnostic tests to measure a persons susceptibility to different diseases may become a distinct reality. Preventative actions such as change of lifestyle or having treatment at the earliest possible stages when they are more likely to be successful, could result in huge advances in our struggle to conquer disease. Gene therapy: In the not too distant future, the potential for using genes themselves to treat disease may become a reality. Gene therapy is the approach used to treat, cure or even prevent disease by

Applications and software Tools for Bioinformatics

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changing the expression of a persons genes. Currently, this field is in its infantile stage with clinical trials for many different types of cancer and other diseases ongoing. Drug development: At present all drugs on the market target only about 500 proteins. With an improved understanding of disease mechanisms and using computational tools to identify and validate new drug targets, more specific medicines that act on the cause, not merely the symptoms, of the disease can be developed. These highly specific drugs promise to have fewer side effects than many of today's medicines. Microbial genome applications: Microorganisms are ubiquitous, that is they are found everywhere. They have been found surviving and thriving in extremes of heat, cold, radiation, salt, acidity and pressure. They are present in the environment, our bodies, the air, food and water. Traditionally, use has been made of a variety of microbial properties in the baking, brewing and food industries. The arrival of the complete genome sequences and their potential to provide a greater insight into the microbial world and its capacities could have broad and far reaching implications for environment, health, energy and industrial applications. For these reasons, in 1994, the US Department of Energy (DOE) initiated the MGP (Microbial Genome Project) to sequence genomes of bacteria useful in energy production, environmental cleanup, industrial processing and toxic waste reduction. By studying the genetic material of these organisms, scientists can begin to understand these microbes at a very fundamental level and isolate the genes that give them their unique abilities to survive under extreme conditions. Waste cleanup: Deinococcus radiodurans is known as the world's toughest bacteria and it is the most radiation resistant organism known. Scientists are interested in this organism because of its potential usefulness in cleaning up waste sites that contain radiation and toxic chemicals. Climate change Studies: Increasing levels of carbon dioxide emission, mainly through the expanding use of fossil fuels for energy, are thought to contribute to global climate change. Recently, the DOE (Department of Energy, USA) launched a program to decrease atmospheric carbon dioxide levels. One method of doing so is to study the genomes of microbes that use carbon dioxide as their sole carbon source. Alternative energy sources: Scientists are studying the genome of the microbe Chlorobium tepidum which has an unusual capacity for generating energy from light.

Applications and software Tools for Bioinformatics

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Biotechnology: The archaeon Archaeoglobus fulgidus and the bacterium Thermotoga maritima have potential for practical applications in industry and government-funded environmental remediation. These microorganisms thrive in water temperatures above the boiling point and therefore may provide the DOE, the Department of Defense, and private companies with heat-stable enzymes suitable for use in industrial processes. Other industrially useful microbes include, Corynebacterium glutamicum which is of high industrial interest as a research object because it is used by the chemical industry for thee biotechnological production of the amino acid lysine. The substance is employed as a source of protein in animal nutrition. Lysine is one of the essential amino acids in animal nutrition. Biotechnologically produced lysine is added to feed concentrates as a source of protein, and is an alternative to soybeans or meat and bonemeal. Xanthomonas campestris pv. is grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying and stabilising agent in many industries. Lactococcus lactis is one of the most important micro-organisms involved in the dairy industry, it is a non-pathogenic rod-shaped bacterium that is critical for manufacturing dairy products like buttermilk, yogurt and cheese. This bacterium, Lactococcus lactis ssp., is also used to prepare pickled vegetables, beer, wine, some bread and sausages and other fermented foods. Researchers anticipate that understanding the physiology and genetic make-up of this bacterium will prove invaluable for food manufacturers as well as the pharmaceutical industry, which is exploring the capacity of L. lactis to serve as a vehicle for delivering drugs. Antibiotic resistance: Scientists have been examining the genome of Enterococcus faecalis-a leading cause of bacterial infection among hospital patients. They have discovered a virulence region made up of a number of antibiotic-resistant genes that may contribute to the bacterium's transformation from harmless gut bacteria to a menacing invader. The discovery of the region, known as a pathogenicity island, could provide useful markers for detecting pathogenic strains and help to establish controls to prevent the spread of infection in wards. Forensic analysis of microbes: Scientists used their genomic tools to help distinguish between the strains of Bacillus anthryacis that was used in the summer of 2001 terrorist attack in Florida with that of closely related anthrax strains The reality of bioweapon creation Scientists have recently built the virus poliomyelitis using entirely artificial means. They did this using genomic data available on the Internet and materials from a mail-order chemical

Applications and software Tools for Bioinformatics

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supply. The research was financed by the US Department of Defense as part of a bio warfare response program to prove to the world the reality of bioweapons. The researchers also hope their work will discourage officials from ever relaxing programs of immunization. This project has been met with very mixed feelings Crop improvement: Comparative genetics of the plant genomes has shown that the organization of their genes has remained more conserved over evolutionary time than was previously believed. These findings suggest that information obtained from the model crop systems can be used to suggest improvements to other food crops. At present the complete genomes of Arabidopsis thaliana (water cress) and Oryza sativa (rice) are available.

Applications and software Tools for Bioinformatics