Genomics: New Aspect of Cancer Research

International Journal of Systems Biology, ISSN: 0975–2900, Volume 1, Issue 1, 2009, pp-01-19

Genomics: New aspect of cancer research

Gomase V.S.*, Tripathi A.K. and Tagore S. *Department of Bioinformatics, Padmashree Dr. D. Y. Patil University, Plot No-50, Sector-15, CBD Belapur, Navi Mumbai, 400614, India; Mail: [email protected]

Abstract - Genomics deals with the study of genes and their function of all organisms. It is that branch of omics that leads to an understanding of the molecular mechanisms of genes, diseases, including the complex interplay of genetic and environmental factors. It is also important in the development of drugs, design of new drugs, vaccines and DNA diagnostics. Genomics-based therapeutics includes traditional small chemical drugs, protein drugs, and gene therapy. It also refers to the large-scale investigation of the structure and function of genes. This field also leads to new drug discovery and development, agricultural sciences and other fields. Keywords - Genome, Metabolome, Metagenomics, Nitrogenomics, Proteome, Cancer research

1. Introduction come into play for many conditions, including Genomics is that branch of omics that deals with many types of cancer. Still, a deeper the study of an organism's entire genome. It understanding of genomics will shed light on involves analysis of intragenomic phenomena, more than just hereditary risks by revealing the viz., heterosis, epistasis and other interactions basic components of cells and, ultimately, between loci and alleles within the genome. It explaining how all the various elements work also includes various strategies for determining together to affect the human body in both health the entire DNA sequence of organisms and fine- and disease (Rossi et al, 2007; Busso et al, scaling the genetic mapping efforts. Also, the 2008; Carlson 2008). aim of this genomic information analysis is to elucidate its effect on and response to the entire 2. History of Genomics genome network. With the vast trove of data This field came into existence in early 1980s. It about human DNA generated by the Human developed at very fast due to some ongoing Genome Project and the HapMap Project, genome projects in the 1990s. Previously, this scientists and clinicians have much more was mainly concerned with sequencing the powerful tools to study the role that genetic genomes of various organisms. But with the factors play in much more complex diseases, growth of this science, the knowledge of full viz., cancer, and cardiovascular disease that genomes has been available for new constitute the majority of health problems today. developments and carries the new field of Genome-based research is already enabling functional genomics, which came into existence. medical researchers to develop more effective This mainly concerned with the patterns of gene diagnostic tools, to better understand the health expression during various conditions. In the year needs of people based on their individual 1972, Walter Fiers and his co-workers at the genetic make-ups, and to design new treatments Molecular Biology unit of the University of for disease. Thus, the role of genomics in health Ghent, Belgium, first determined the sequence care and medicine is starting to change for bacteriophage MS2 coat protein gene. In profoundly. The first examples of this era are the 1976, the team determined the complete use of personalized medicine. It is important to nucleotide-sequence of bacteriophage MS2- realize, however, that it often takes considerable RNA. Frederick Sanger in the year 1977 time, effort, and funding to move discoveries sequenced the first DNA-based genome of from the scientific laboratory into the medical bacteriophage Φ-X174. The first free-living clinic. Most new drugs based on genome-based organism to be sequenced was that of research are estimated to be at least 10 to 15 Haemophilus influenza in 1995. In early 2000, years away. Screening and diagnostic tests, the human genome was completed by the however, are expected to arrive more quickly. Human Genome Project. The complete Rapid progress is also anticipated in this field. sequence was known of about 1879 viruses, Clearly, genomics remains just one of several 577 bacterial species and roughly 23 eukaryote factors that contribute to people's risk of organisms, of which about half are fungi on developing most common diseases. Diet, 2007. The worm Caenorhabditis elegans is an lifestyle, and environmental exposures also often used simple model for multicellular

Genomics: New aspect of cancer research

organisms. The Japanese pufferfish ( Takifugu bacterial artificial chromosomes (BACs), rubripes ) and the spotted green pufferfish because it could be inserted into bacteria, where (Tetraodon nigroviridis ) are also interesting they could be copied by the bacterial DNA because of their small and compact genomes, replication machinery. Each of these pieces was containing very little non-coding DNA compared then sequenced separately as small ‘shotgun’ to most species. Most of the bacteria whose project and then assembled. The larger, 150,000 genomes have been completely sequenced are base pairs went together to create problematic disease-causing agents, such as chromosomes. This was termed as the Haemophilus influenza . The mammals, dog hierarchical shotgun approach. This was so (Canis familiaris ), brown rat ( Rattus norvegicus ), because the genome was first broken into mouse ( Mus musculus ), and chimpanzee ( Pan relatively large chunks, which were then mapped troglodytes ) are also important model animals in to chromosomes before being selected for medical research. The zebrafish (Brachydanio sequencing. The widespread international rerio ) is also used for many developmental cooperation and advances in the field of studies on the molecular level and the flower genomics and sequence analysis along with Arabidopsis thaliana is a model organism for development in computation, the 'rough draft' of flowering plants (Weckwerth 2008; Bottcher et the genome was finished in 2000. These drafts al, 2008; Dacks et al, 2008). covered about 83% of the genome. In February 2001, at the time of the joint publications, press 3. The Genomics Project releases announced that the project had been. The Human Genome Project completed in 2003, Improved drafts were announced in 2003 and which is coordinated by the U.S. Department of 2005, filling into ~92% of the sequence currently. Energy and the National Institutes of Health. The The last chromosome was published in the goals were a) identifying all the genes in human journal Nature, on May 2006. Along with this DNA, b) determining the sequences of the 3 project, in 1998, a similar, privately funded quest billion chemical base pairs that make up human was launched by Craig Venter and his firm DNA, c) storing this information in databases, d) Celera Genomics. It was a $300 million project improving tools for data analysis; transferring that was intended to proceed at the faster and at related technologies to the private sector and fractions of the cost of the roughly $3 billion addressing the ethical, legal, and social issues publicly funded project. The technique known as (ELSI) that may arise from the project. The whole genome shotgun sequencing that had project began in 1990 initially headed by James been used to sequence bacterial genomes of up D. Watson, who was head of the National to six million base pairs in length, but not for Center for Human Genome Research at the anything nearly as large as the three thousand National Institutes of Health (NIH) in the United million base pair human genome by Celera States starting from 1988. But, due to his Genomics. Thus, the Human Genome Project is disagreement with Bernadine Healy over the the most well known of many international issue of patenting genes, he was forced to genome projects that aimed at sequencing the resign in 1992. He was replaced by Francis DNA of a specific organism, which offered the Collins in April 1993, and the name of the Center most tangible benefits, important developments was changed to the National Human Genome in biology and medicine. This are predicted the Research Institute (NHGRI) in 1997. A working result of sequencing of model organisms for draft of the genome was released in 2000 and a example, mice, fruit flies, zebrafish, yeast, complete one in 2003. Most of the sequencing nematodes and others (Suarez et al, 2007; was performed in research institutes and Cattley et al, 2007; Lyle et al, 2007; Comai universities from the USA, UK, along with 2007). geneticists from China, France, Germany and Japan. The objective of the Human Genome 4. Genomics strategies Project was to understand the genetic makeup In Bacteriophage Genomics Strategies, of the human species; it has also focused on bacteriophages have been playing a key role in several other nonhuman organisms, i.e. bacterial genetics and molecular biology. These Escherichia coli . The roots of the project started are previously used for defining gene structure from the early work on the inheritance of traits, and regulation. The first genome sequence of like those in plants. The genome was broken bacteriophage did not lead the genomics into smaller pieces; approximately 150,000 base revolution, which is further dominated by pairs in length. These pieces were termed as bacterial genomics. After the prominence of

International Journal of Systems Biology, ISSN: 0975–2900, Volume 1, Issue 1, 2009 2 Gomase VS, Tripathi AK and Tagore S

bacteriophage genomes analysis, researchers field for popularizing the technology to common started to understand the mechanisms people. It’s main goal to sequence as many underlying phage evolution. The bacteriophage people as possible for large scale comparative genome sequences obtained through direct genomics analysis. Once a great number of 3 sequencing of isolated bacteriophages. In some billion bases of individuals are collected, human case, this can derived as part of microbial genetic diversity could be completely mapped genomes, also analysis of bacterial genomes (Bush 2007). shows the substantial amount of microbial DNA consists of prophage sequences and prophage- 5. Genomics Technology like elements (Cheng et al, 2007; Powers 2007). 5.1. Analytical technologies: Separation In Cyanobacteria Genomics Strategies having techniques total 24 cyanobacteria for which a total genome 5.1.1 Gas chromatography (GC) sequence are available. Out of this, 15 A common problem in the omics field is the originated from the marine environment. Study consolidation of signal list derived from demonstrated that the various sequences used metabolic profiling of different cell or tissue or for inferring various physiological and ecological fluid states where a number of replicate characteristics of marine cyanobacteria and experiments was collected on each state. It is an thus, the growing body of genome information approach for the consolidation of peak list based also used for addressing global problems by on hierarchical clustering, first within each set of applying a comparative genomics (Ikegawa replicate experiments and then between the sets 2007; Maeda 2007). Computational genomics of replicate experiments. The problems of Strategies deciphering biology from genome finding the dendrogram tree cutoff, which gave sequences using computational analysis. It the optimal number of peak clusters and the mainly focuses on understanding the human effect of different clustering methods. This genome and the principles for DNA control approach is applied to gas chromatography- biology of any organisms at the molecular level. mass spectrometry metabolic profiling data, Computational simulation is applicable for most which are acquired on Leishmania mexicana. important means to biological discovery for the Analysis result into robust data matrices, which current abundance of massive biological completely separated the wild-type and two datasets. The various role performed by this mutant parasite lines based on their metabolic techniques including discovering subtle patterns profile (De Souza et al, 2006). Over the past in genomic sequences, proposing cellular decade, genomics has undergone a rapid signaling networks, proposing mechanisms of development and radiation, diversifying across genome evolution, predicting precise locations the biochemical landscape. Targeted of all human genes using techniques with approaches, profiling strategies using affinity several mammalian and vertebrate species, capture mass spectrometry and solution array predicting conserved genomic regions that are represented realistic opportunities to deliver related to early embryonic development, predictive capacity. Many recent applications in discovering potential links between repeated genomic and peptide profiling, viz., solid-phase sequence motifs and tissue-specific gene affinity capture mass spectrometry and the expression and measuring regions of genomes targeted approach of antibody arrays have also that have undergone unusually rapid evolution arose for gene expression analysis (Rice et al, (Legato 2007; Manning et al, 2007). 2006). Predictive metabolite profiling based on Nitrogenomics Strategies involves the study of resolution of GC-MS data followed by genomics pertaining to nitrogen utilization and multivariate data analysis applied to three assimilation in organisms. The genomics of different biofluid data sets. Hierarchical nitrogen assimilation lie at different levels of multivariate curve resolution (H-MCR) is used to organisms from microbes to higher organisms, simultaneously resolve the GC-MS data into where different genetic controls regulate the pure profiles. Analysis presented an extension of actual assimilation (Beyer et al, 2007; Cobourne the H-MCR method allowing treatment of 2007). Metagenomics Strategies invloves the independent samples according to processing study of genetic material recovered directly from parameters estimated from a set of training environmental samples. This enables the study samples. Predictions of the new samples are of organisms that are not easily cultured in a based on their metabolite profiles, into an laboratory as well as their natural environment existing model, which is the requirement for a (West 2007). Personal genomics Strategies is a working application with clinical diagnosis.

Genomics: New aspect of cancer research

Method also reduced the time for curve characterization of changes in protein resolution process, which only a subset of phosphorylation on extracts from HeLa cells representative samples, while the remaining treated with or without calyculin A, a potent PPP samples could be treated according to the enzyme inhibitor. For this, a label-free obtained processing parameters (Jonsson et al, comparative phosphoproteomics approach using 2006). immobilized metal ion affinity chromatography and targeted tandem mass spectrometry was 5.1.2 High performance liquid employed to discover and identify signatures chromatography (HPLC) based upon distinctive changes in abundance. Liquid chromatography- mass spectroscopy ( LC- 232 proteins are identified as either direct or MS) platform is used in large peptide analysis indirect targets for PPP enzyme regulation for combining collision-induced dissociation (Yang et al, 2007). (CID), electron-transfer dissociation (ETD) and CID of an isolated charge-reduced (CRCID) 5.2. Analytical technologies: Detection species derived from ETD, which is determine techniques the sites of phosphorylation and glycosylation 5.2.1 Magnetic resonance imaging (MRI) modifications. The prediction of large peptide Genomics, proteomics and metabolomics offers fragments sequence can possible from complex unique ways for probing internal mechanisms of proteins, i.e. beta-casein, tissue plasminogen cancer. The study of the global variation of activator (t-PA) at low femtomol level. It was metabolites involved in the development and found that after the incorporation of an additional progression of cancers nuclear magnetic CID activation step for a charge-reduced resonance (NMR), which is quite a useful species, isolated from ETD fragment ions, technique. The most fundamental magnetic improved ETD fragmentation when precursor resonance methodologies with regard to human ions with high > 1000 m/z were automatically prostate cancer are magnetic resonance selected for fragmentation. Also, the spectroscopy and magnetic resonance identification of the exact phosphorylation sites spectroscopic imaging. It has been seen that is strengthened by the extensive coverage of the some crucial metabolites could indicate peptide sequence with a near-continuous cancerous lesions and have the potential to product ion series. This strategy provided good direct treatment (Jordan et al, 2007). Scientists starting survey scan for characterizing demonstrated the biological basis of cancer at enzymatic peptide mixtures over a broad range the molecular level. It is quite possible to model of masses using LC-MS with data-dependent the process of cancer and identify the points at acquisition. The new LC-MS platform is useful which therapeutics could operate. Genomic approach for the comprehensive analysis also added to conventional characterization of complex proteins and pharmacokinetics, pharmacodynamics in genomes (Wu et al, 2007). The derivatization of preclinical models and at selected points in cysteine-containing peptides with benzoquinone clinical development; but advancement in compounds is rapid, quantitative and specific in functional imaging made this an important tool acidic media. During liquid chromatography for assessing response to therapy. Functional separation shows the conversion of cysteines analyses of computed tomography (CT) and into hydrophobic benzoquinone-adducted magnetic resonance imaging (MRI) images also residues for altering the chromatographic added important information about tumour properties of cysteinyl peptides. The patho-physiology, positron emission tomography benzoquinone derivatization allow the accurate (PET) and single photon emission tomography selection of cysteine-containing peptides of (SPECT) imaging that made it possible to study bovine serum albumin tryptic digest by diagonal the distribution and therapeutic function of drugs reversed-phase chromatography, which (Begent 2007). Genomics, proteomics and consisted of one primary and a series of metabolomics leased fresh life in new era of secondary identical liquid chromatographic biomedical discovery that is already affecting separations, before and after a cysteinyl- every field of medicine. With their rapid growth targeted modification of the peptides by there is great interest in applying these benzoquinone compounds (Dayon et al, 2007). technologies not only to diagnose and prevent For identification of phosphoproteins regulated disorders, but also to enhance brain longevity by the phosphoprotein phosphatase (PPP) and mental wellness. Nearly two-thirds of the family of S/T phosphatases, large-scale total genes in the human genome are found to

International Journal of Systems Biology, ISSN: 0975–2900, Volume 1, Issue 1, 2009 4 Gomase VS, Tripathi AK and Tagore S

relate to the brain functions and up to half of the The announcement of the birth of Dolly in late variance in age-related changes in cognition; in 1990s additional sheep, cows, goats, pigs and which brain volume and neuronal function mice were cloned. Cloning was found to be appeared to be genetically determined (Petrella attractive, which reduced the effort and time et al, 2008). needed for farmers to do what they have been doing for years: selecting and propagating the 5.2.2 Mass spectrometry (MS) best of the herd. The significance of the first Advances in genomics technologies in the last cloned mammal achieved from an adult cell. decade; mass spectrometry has emerged as the One cell, the fertilized egg, contains all of the preferred method for in-depth characterization of information needed to multiply and give rise to the various components of biological systems. all of the specialized cells in the body. Cells turn In-depth understanding of the composition, on and off different genes as they become regulation and function of molecular complexes specialized. In cloning differentiated cell and pathways has been gained. It is clear that reprograms or resets its genetic information so mass-spectrometry-based techniques are vary that it acts as a fertilized egg. Cloning has powerful hypothesis-generating engine, which opened many doors, which could lead to combined with complementary molecular, remarkable medical advancements but, as with cellular and pharmacological techniques, all new technologies, it would be accompanied provided a framework for translating large data by ethical and social dilemmas. Today's sets into an understanding of complex biological successes would pave the road to improving processes (Cravatt et al, 2007). Genomics and efficiencies and help add to the basic proteomics have grown significantly with the aid understanding of our cells (Seam et al, 2007). In of new technologies that were becoming more the mid-1980s researchers began to examine streamlined. While processing of proteins from a the promises of gene-therapy through logical whole cell lysate have typically done in a and straightforward solution to genetic disease, bottom-up fashion utilizing MS/MS of peptides i.e. if a gene seemed to be causing a disease, from enzymatically digested proteins. Top-down then to cure the disease scientists must remove proteomics and genomics is becoming a viable the bad gene and substitute a good gene. alternative that has limited largely to offline Hundreds of gene therapies protocols exist, one analysis by tandem mass spectrometry. few have been approved for human trials. Gene Scientists explained a method for high-resolution therapy has yet to fulfill its promise of curing any tandem mass spectrometry of samples on a genetic disease. Human gene therapy chromatographic time scale. Single liquid experimentation raised many issues and chromatography-tandem mass spectrometry promises to the technology, which is (LC-MS/MS) identified 22 yeast proteins with represented as very great and the reality of molecular weights from 14 to 35 kDa. Using dangerous. It has been found the for a better anion exchange chromatography to fractionate gene therapy, some of the given criteria protocol whole cell lysate detected 231 metabolically must be followed, i.e. to reappraise the current labeled (14N/15N) protein pairs from framework and structure of gene therapy Saccharomyces cerevisiae . This is the first research, to reexamine informed consent demonstration of top-down proteomics and procedures and to take public responsibility for genomics on linear ion trap Fourier transform their actions (Bottero et al, 2004). Another use of (LTQ FT) systems using high-resolution MS/MS genomics is in the case of transgenic organisms. data obtained on a chromatographic time scale A transgenic organism is any living creature, (Parks et al, 2007). Tandem mass spectrometry such as a bacterium, plant, or animal that coupled to liquid chromatography (LC-MS/MS) received a foreign gene by means of genetic allowed identification of biological samples in a engineering. There are many applications for complex mixture without need for sample transgenic organisms in the health and food purification. Progress in LC-MS/MS-based industries. Scientists developed a variety of quantification, phosphoproteomic analysis, and transgenic silkworms that spin industrial-strength targeted LC-MS/MS using multiple reaction or glow-in-the-dark fibers, for example, or make monitoring (MRM) has made LC-MS/MS a silk with human proteins. A mosquito could also powerful tool for studying cell physiology be engineered to be unable to carry one type of (Pisitkun et al, 2007). malaria parasite. Field tests are underway to determine the safety of using transgenic pink 5.4. Genomics in practice bollworms, designed to spread sterility to wild

Genomics: New aspect of cancer research

bollworms, to protect agricultural crops. Most to the most distal breakpoint and 17q24.1, a transgenic research are still in the development region coinciding with breakpoints leading to phase and now is the time to address the impact superimposed gain (Vandesompele et al, 2008). of transgenomics on the environment, crop production and animal and human health 5.5.3 Functional Genomics (Hinkelbein et al, 2007). Sorghum is one of the more allelopathic crop species that produced phytotoxins, viz., 5.5. Technology development in Genomics benzoquinone sorgoleone and its analogs. and approaches Sorgoleone accounted for much of the 5.5.1 Data mining allelopathy of Sorghum spp., representing the Emerging statistical concepts like data mining predominant constituent of Sorghum bicolor root techniques can be use for genomic data exudates. The biosynthetic pathway for this analysis. A novel concept of statistical plant growth inhibitor occurred in root hair cells, significance, called false discovery rate the rate which involved a polyketide synthase activity of false-positives among all positive findings that utilizing an atypical 16:3 fatty acyl-CoA starter has suggested controlling the error rate of unit, resulting in the formation of a numerous false-positives in large screening pentadecatrienyl resorcinol intermediate. biological data analysis. Statistical modeling in Analyses is performed by gas chromatography- genomic data analysis have been presented, mass spectrometry with sorghum root extracts viz., analysis of variance and heterogeneous identified a 3-methyl ether derivative of the likely error modeling approaches for analyzing pentadecatrienyl resorcinol intermediate, microarray data obtained from multiple indicating that dihydroxylation of the resorcinol experimental or biological conditions. Other ring is preceded by O-methylation at the 3'- machine learning tools such as supervised position by a novel 5-n-alk(en)ylresorcinol- learning and unsupervised learning have also utilizing O-methyltransferase activity. been used. The former approach included Quantitative real time reverse transcription-PCR several multivariate statistical methods to and recombinant enzyme studies with putative investigate co-expression patterns of multiple O-methyltransferase sequences obtained from genes, and the latter were the classification the expressed sequence tag data set is led to methods to discover genomic biomarker the identification of a novel O-methyltransferase signatures for predicting important subclasses of highly and predominantly expressed in root human diseases (Lee et al, 2008). hairs, which preferentially utilizes alk(en)ylresorcinols among a panel of benzene- 5.5.2 Integrative genomics derivative substrates tested (Baerson et al, The partial gain of chromosome arm 17q is the 2008). most frequent genetic change in neuroblastoma (NB) and constituted the strongest independent 5.5.4 Comparative genomics genetic factor for adverse prognosis. Applied DNA microarray hybridization compared the chromosome 17 tiling path BAC arrays on a genome content of Streptomyces avermitilis , panel of 69 primary tumors and 28 NB cell lines Streptomyces cattleya, Streptomyces maritimus in order to reduce the current smallest region of and Kitasatospora aureofaciens with that of gain and facilitate identification of candidate Streptomyces coelicolor A3(2), which showed dosage sensitive genes. In all tumors and cell about 93% agreement with the genome lines with 17q gain, large distal segments are sequence data available for S. avermitilis . It also consistently present in extra copies and no showed a number of trends in the genome interstitial gains are observed. Positional gene structure for Streptomyces and closely related enrichment analysis for 17q genes over- Kitasatospora. A core central region is found to expressed in NB also showed that dosage be conserved that could be predicted from sensitive NB oncogenes are most likely located previous research and is linked to a low degree in the gained region immediately distal to the of gene conservation in the terminal regions of most distal breakpoint of the 2 breakpoint the linear chromosome across all four species. regions. Comparison of gene expression profiles Between these regions there are two areas of between primary tumors and normal fetal intermediate gene conservation by microarray adrenal neuroblasts revealed two gene clusters analysis where the gene synteny is still on chromosome 17q that were over-expressed detectable in S. avermitilis (Hsiao et al, 2008). in NB, i.e. region on 17q21.32 immediately distal

International Journal of Systems Biology, ISSN: 0975–2900, Volume 1, Issue 1, 2009 6 Gomase VS, Tripathi AK and Tagore S

6. Applications of Genomics identification of putative genes based on the Genomics has been applied in many diverse combined in vitro protein synthesis with mass fields. This includes agriculture and drug spectrometry. For the rapid identification of production, where not only can the best traits be functional activity of unknown genes from a perpetuated but farm animals could also be sequence database, a new method based on in used as machines for large-scale production of vitro protein synthesis combined with mass medically important proteins. A transgenic spectrometry was developed (Kim et al, 2008). cloned lamb is able to produce milk containing This comparative genomics study of human vs. factor IX - the protein that is deficient in insects sheds light on the composition and haemophiliacs. Genomics has also been applied assembly of protein complexes in the synapse for maintaining biodiversity. Cloning may be an gives the nature of the protein-interaction important tool for preserving endangered graphs, their domain composition and the species if currently practiced methods fail. sequence similarity between human and insects Biomedical Research is also an important area differentiate exocytotic from endocytotic proteins where genomics studies are performed. Cloning and suggest unique evolutionary constraints for and other strategies could produce genetically each group. The design of proteins of the identical laboratory animals which can be used presynaptic site can be studied from a as models for human disease. The most comparative genomics perspective on human commonly used laboratory animal, the mouse, and insects (Yanay et al, 2008). The importance reproduces rapidly and its genetics is well of trehalose metabolism and its role in plants studied. A mouse was successfully cloned and have gone through something of a revolution. will likely facilitate the discovery of new Trehalose metabolism and signaling is an area treatments for disease. In addition, it provides a of emerging significance; mutant and transgenic model for studying the interaction of nuclear plants of trehalose synthesis display wide- verses mitochondrial genes and for nuclear ranging and unprecedented phenotypes for the verses cytoplasmic factors. Some commercial perturbation of a metabolic pathway. Molecular endeavours have been performed too. physiology and genomics have provided a Researchers got little success in the steps glimpse of trehalose biology that had not been required to make a dog clone, such as possible with other conventional techniques due development after nuclear transfer and embryo to because the products of the synthetic implantation into the womb. Much human pathway, trehalose 6-phosphate (T6P) and disease treated using this area of research. trehalose, are in trace abundance and difficult to Cells can harvested from early embryos to measure in most plants (Paul et al, 2008). Perch provide cell and tissue replacement without the are promising species for freshwater hazards of transplantation rejection (Dieterle et aquaculture and, differently from other fish and al, 2008; Liu et al, 2008). show a wide genetic variability that is undesirable for aquaculture. EST cataloguing 7. Current Research and profiling of perch will provide a basis for The availability of multiple teleost (bony fish) functional genomic research in this species and genomes is providing unprecedented also promote studies in comparative and opportunities to understand the diversity and environmental genomics, for identifying function of gene duplication events using polymorphic markers that are useful; the disease comparative genomics (Howarth et al, 2008). resistance of fish and for discovering of new Chronic toxicities attributed to botanical dietary molecular markers of exposure. Using genomic supplements may be caused by contamination resources of Perch will give immediate and by heavy metals, pesticides, microbes or by practical benefits in the field of aquaculture, inherent properties of constituents of the allowing early diagnosis of the fish conditions botanicals themselves. These chronic toxicity and helping in the generation of new problems may be prevented by implementing mechanistic data on the nature of fish responses good agricultural practices and good to different farming conditions (Rossi et al, manufacturing practices and applying existing 2008). Genomics analysis can provide the basis toxicity testing similar to those used in drug for understanding the evolution of emerging, development or new toxicity assays under lethal human pathogens such as Legionella development based on proteomics, genomics, or pneumophila , the causative agent of metabolomics (van Breemen et al, 2008). A Legionnaires' disease. Genomic also revealed functional genomics is used for rapid functional that L. pneumophila is a genetically diverse

Genomics: New aspect of cancer research

species, in part due to horizontal gene transfer mineral nutrient and trace element composition of mobile genetic elements among L. of an organism and represents the inorganic pneumophila strains, but also between different component of cellular and organismal systems. Legionella species. The genomic background Ionomics is the study of the ionome, involves the also plays a role in disease causation as quantitative and simultaneous measurement of demonstrated by the identification of a globally the elemental composition of living organisms distributed epidemic strain exhibiting the and changes in this composition in response to genotype of the sequenced L. pneumophila physiological stimuli, developmental state, and strain (Cazalet et al, 2008). Diabetic genetic modifications. Ionomics has the ability to nephropathy occurs in only a few patients with capture information about the functional state of diabetes, it is the major cause of end-stage renal an organism under different conditions, which is disease in the world. Hyperglycemia and driven by biotic and abiotic factors. Ionomics is hypertension are important factors predisposing the potential tool to provide a powerful approach patients to diabetic nephropathy, but to not only the functional analysis of the genes accumulating evidence points to critical genetic and gene networks that directly control the factors predisposing only a subset of patients ionome, but also to the more extended gene with diabetes to nephropathy. Comparative networks that control developmental and genomics using the robust genetic reagents physiological processes that affect the ionome available in laboratory mice should provide a indirectly (Salt et al, 2008). Hepatocellular complementary approach to defining genes that carcinoma (HCC) is a worldwide health issue may predispose to diabetic nephropathy in mice that has started receiving attention but similar to and humans. This new studies to identify genetic most types of cancer, hepatocarcinogenesis is a risk factors for diabetic nephropathy and the multistep process involving different genetic unique approaches that may be used to alterations that ultimately lead to malignant elucidate the genetic pathogenesis of this transformation of the hepatocyte. As technology disorder in mice (Breyer et al, 2007). Genome advances and research continues, the genetic sequencing of different strains demonstrates changes and influences among these entities enormous interest in the genetic and metabolic will prove essential to improved diagnostic and diversity of bacteria. Plasmids with an enormous therapeutic options. It remains a challenge to size range are also widespread in the provide a clear picture of the connection Roseobacter clade indicating an adaptive between virus and cancer and providing a genomic structure. Comparisons with other direction for future research and treatment (Tan highly relevant groups, like the SAR11 clade, et al, 2008). Phylogenetic and primary sequence have shown drastic differences in genome characterization of cathepsin B cysteine organization. Physiological characteristics and proteases were studied from the oxymonad the different isolation sources indicate that flagellate monocercomonoides. Comparative organisms of the Roseobacter clade occupy genomics, sequence alignment analysis and various ecological niches (Brinkhoff et al, 2008). phylogenetics are used for cathepsin sequences Genomics technologies are disruptive yet analysis, which help to study the diversity of potentially cost-effective because they enable eukaryotes demonstrated that absence of the primary prevention, the antidote to runaway occluding loop is not a feature exclusive to costs and declining productivity in health care. oxymonads, but is relatively common, Many bioethical and social-policy implications suggesting that the occluding loop should no are alarming (Carlson 2005). Genomics study longer be used as the defining feature of the demonstrates the necessity of whole-genome cathepsin B subfamily (Dacks et al, 2008). analysis to complement population and gene- Levels of cytochromes P450 and especially drug based studies, which are of limited utility in transporters due to inflammation in brain, uncovering complex events such as intestine, and placenta have significant recombination that may lead to functional implications for the use of many drugs in diverse differences in virulence and pathogenicity. The clinical settings. The development of mouse advancement of comparative genomics of models of live bacterial infection provides human pathogens and emerging disease in wild excellent opportunities to explore the impact of populations of endangered species are infection on drug metabolism beyond the well applicable in the analysis of full-length lion characterized effects of bacterial endotoxin. lentiviruses (Pecon-Slattery et al, 2008). The Repression of drug clearance pathways by ionome is science which can define as the cancer cytokines may result in extreme toxicity

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to chemotherapy, compromising treatment of miRNAs play prognostic value in predicting many cancers (Morgan et al, 2008). Induction of clinical behaviors of cancer patients drug enzyme activity in the intestine can strongly (Giannakakis et al., 2007; Nervi et al., 2008; determine plasma levels of drugs. It is important Bertucci and Birnbaum 2008; Yang et al., 2008). to predict drug-drug interactions in human They are important regulatory molecules in intestine in vitro. The study shows that human plants and animals. miRNA, by translational intestinal precision-cut slices are useful to study repression, mRNA cleavage, and mRNA decay induction of drug-metabolizing enzymes and initiated by miRNA-guided rapid deadenylation. transporters in the human intestine (van de Some miRNAs regulate cell proliferation and Kerkhof et al, 2008). It's also possible that genes apoptosis processes that are important in cancer not directly involved in a particular pathway formation. By using multiple molecular could end up being predictive of clinical techniques, which include miRNA microarray, outcomes. Although pharmacogenomics has the Northern blot analysis, real-time PCR, up or potential to radically change the way health care down-expression of specific miRNAs, it was is provided, it is only in its infancy. In the future, found that several miRNAs were directly pharmacogenomics could find uses along the involved in human cancers, including brain, liver, entire drug discovery and development timeline, lung, breast, colon cancer and leukemia ( Zang, all the way from target discovery and validation et al., 2007). to late-stage clinical trials (Gomase et al, MicroRNAs altered in human tumors, both 2008a). Bioinformatics is being increasingly oncogenic and tumor suppressive potential and used to support target validation by providing aslo involvement in the pathophysiology of brain functionally predictive information mined from cancer. miRNA germline, somatic mutations and databases and experimental datasets using a polymorphisms in the protein coding messenger variety of computational tools (Gomase et al, RNA targeted by miRNAs contributing to cancer 2008b). predisposition, initiation and progression. In somatic cells, miRNA alterations may play a role 8. New aspect of cancer research in tumor initiation, while if present in germ line 8.1 MicroRNAs (miRNAs) cells they could constitute a cancer predisposing MicroRNAs are a new class of endogenous, event. miRNA fingerprinting is the diagnostic non-coding, small RNAs, which negatively and prognostic tools used by medical regulate gene expression in a sequence-specific oncologists. New therapeutic strategies involving manner. They can act via translational miRNA silencing or miRNA mimics could be repression or mRNA degradation. MicroRNAs proposed based on the roles of these small non- discovery revealed a new and exciting aspect of coding RNAs as oncogenes and tumor post-transcriptional gene regulation, which is suppressors in brain tumors. The discovery of universally involved in cellular homeostasis. The miRNAs interact with known oncogenes has advent of miRNAs added another level of established further links with molecular complication in the already complex regulatory pathways implicated in malignant networks of the cell and should be considered transformation. miRNAs can used as diagnostic gene regulators of equal importance with markers and their potential as therapeutic proteins. Now researchers attention to the molecules has moved miRNAs from the area of miRNA field for an additional reason: an basic research to the field of tumor increasing line of evidence indicated that miRNA biotechnology. The mechanisms of mRNAs of genes are tightly connected with the process of tumor suppressor- and oncogenes i.e. gross tumorigenesis. Many miRNAs genes genomic aberrations, epigenetic changes, and demonstrated to behave as oncogenes or tumor minor mutations affecting the expression level, suppressor genes in many types of cancer. The processing and target-interaction potential of the mechanisms by which miRNAs can destabilize miRNA. Expression profiling of miRNAs has the normal cellular processes, promoting cell been found to be useful for classification of transformation and tumor progression play a different tumor types and classified as onco- critical role. New technologic use the profiling of miRs or tumor suppressor-miRs and may turn the miRNA expression patterns in normal and out to be potential targets for cancer therapy cancer tissues and discovered unexpected (Esteller 2008; Negrini et al., 2007; Cowland et greater reliability of miRNA expression al., 2007; Nicoloso and Calin 2007). signatures in classifying cancer types than the respective signatures of protein-coding genes. 8.2 SNP and Genetic association

Genomics: New aspect of cancer research

The development of DNA chip technology has a basis for DNA-based cancer classification and significant impact on the genetic analysis of help to define the genes being modulated, human disorders. The newly developed single improving understanding of cancer genesis and nucleotide polymorphism (SNP) array can use to potential therapeutic targets (Glinsky 2008b; measure both DNA polymorphism and dosage Dutt and Beroukhim 2007; Gomase et al., recomondations. SNP microarray analysis to 2008c) uncover frequent uniparental disomies and sub- microscopic genomic copy number gains and 8.3 Transcriptomics in cancer research losses in different cancers. SNP array genotye A wealth of evidence has pointed to dietary can determine loss of heterozygosity, genomic habits as a determinant of premature death, copy number changes and DNA methylation including that associated with heart disease, alterations of cancerous cells. It can be applied stroke, diabetes, liver disease, atherosclerosis to the identification of cancer predisposition and cancer. Nutritional genomics refers to the genes, oncogenes and tumor suppressor genes bidirectional interactions between diet and in specific types of tumors. Variations in DNA genes. Nutritional genomics encompasses an sequences associated with multiple human understanding about how the response to disorsers may affect phenotypes in trans via bioactive food components depends on an non-protein-coding RNA intermediaries individual's genetic background i.e. interfering with functions of microRNAs. It nutrigenetics. Nutrient induced changes in DNA defines the nuclear import pathway as a methylation, histone posttranslational potential major target in many human diseases modifications, and other chromatin alterations (Mao et al., 2007; Glinsky 2008a). (e.g.- nutritional epigenetics) and nutrient A genome-wide association study reveals a induced changes in gene expression known as structural feature of sncRNA sequences and nutritional transcriptomics. Nutritional human microRNAs. These features are useful transcriptomics study of nutrition will assist in for multiple seemingly unrelated sncRNA understanding how genetic variation, epigenetic pathways points to a multitude of potential events and regulation of gene expression alter functional and regulatory implications. It involves requirements for, and responses to nutrients. mechanisms of gene expression regulation, Genes and diet could ultimately help identify control of biogenesis, stability and bioactivity of modifiable molecular targets for preventing, microRNAs, sncRNA-guided macromolecular delaying and reducing the symptoms of cancer interactions and transcriptional basis of self or and other chronic disorders. High-throughput non-self discrimination by immune system. Non- profiling applications are increasingly used and protein-coding transcripts are contributing to may now even be considered standard research phenotype-defining regulatory and structural tools. Transcriptomics technologies for potential features of a cell. The RNP complexes of biomarkers prediction profiling studies have in sncRNAs of a cell suggesting that informasomes turn attracted the attention of basic researchers represent the intracellular structures, which eager to uncover biological mechanisms provide the increasingly complex structural underlying clinically useful signatures. In specific framework of genomic regulatory functions in transcriptomics are use for gene expression higher eukaryotes to facilitate the stochastic, datasets and most current applications in breast random and probabilistic mode of choices in a cancer research. Use of transcript profiles is to sequence of regulatory events defining the define the molecular signature of diseases e.g. phenotype. SNP arrays provide a high-resolution cancer and transcriptomics has used to study platform for describing several types of genetic intestinal biology (Ross 2007; Culhane and changes simultaneously. This array increasing Howlin 2007; Fleet 2007; Schäfer et al., 2007 ). powerful tools for describes the genetic events Interrelationship between the food components cancer. The ability to determine allele-specific and the 'omics techniques' (transcriptomics, copy number changes has only recently been proteomics, genomics, epigenomics and described by SNP array and offers a high- metabolomics) have a significant influence on throughput platform for large-scale association the quality of life as measured by both physical studies that are likely to lead to the identification and cognitive performance and modify the risk of multiple germline variants, which predispose and severity of a variety of cancer diseases to cancer. SNP arrays are an ideal platform for conditions (Milner 2007; He 2006; Puskás et al., identifying both somatic and germline genetic 2006; Fan et al., 2006; Miles et al., 2006; Davis variants that lead to cancer. Techniques provide and Milner 2004).

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et al., 2005; Gusev and Brackett 2007; Jain 8.4 Role of Pharmacogenomics 2005; Kang and Saif 2008). Applications of Pharmacogenomics to medicine have a long history and the pace of new 8.5 Epigenomics a rode of cancer treatment applications has accelerated in recent decades. Epigenetic mechanisms affecting chromatin Increased investment in science and technology structure contribute to regulate gene expression to stimulate a more vigorous and competitive and assure the inheritance of information, which research environment, development of more are essential for the proper expression of key effective basic and clinical research synergies, regulatory genes in healthy cells, tissues and recruitment and training of more human organs. Epigenomics factors such as DNA resources in genomic medicine, developing methylation and histone deacetylation are mechanisms to stimulate translational research contribute to the malignant transformation of and developing a more modern regulatory cells by silencing critical genes. Some drugs framework to ensure, which genomic medicine inhibit DNA methyltransferases or histone will successfully contribute to improve deacetylases are shown to have the potential to healthcare. The treatment of breast cancer with reactivate silenced genes and induce selective estrogen receptor modulators such as differentiation or apoptosis of malignant cells. tamoxifen and with aromatase inhibitors Histone deacetylase inhibitors are the class of represents new applications in cancer epigenetic modifying agents, which include chemotherapy. The pharmacogenomics depsipeptide, butyrate derivatives, ofaromatase inhibitors including the application suberoylanilide hydroxamic acid and valproic of a genotype to phenotype research strategy acid. Epigenetic events affect various genes and designed to explore the nature and extent of cellular pathways in a non-random fashion and common DNA sequence variation, which can predispose to induction and accumulation of encodes aromatase. A genetic variation in the genetic changes in the course of tumour CYP19 gene is important in the activity of initiation and progression. These considerations aromatase inhibitors and emphasis is on are critical for a better understanding of examining multiple genes in pharmacodynamic tumourigenesis and molecular events underlying and pharmacokinetic pathways in women the acquisition of drug resistance as well as receiving aromatase inhibitors for breast cancer development of novel strategies for cancer (Weinshilboum 2008; Ingle 2008; Jimenez- therapy and prevention (Oki and Issa 2006; Sanchez et al., 2008; Johnson 2008). miRNA Leone et al., 2008; Sawan et al., 2008; Baylin molecular diagnostics, pharmacogenomic and and Chen 2005; Rothhammer and Bosserhoff clinical laboratory molecular services introduce 2007, Sigalotti et al., 2007; D'Alessio and Szyf next-generation miRNA-based diagnostic 2006; Smith et al., 2007; Grønbaek et al., 2007). assays to improve tumor classification, monitor disease progression and potentially allow earlier 8.6 Metabolomics detection of cancer. These new technologies Integration of novel agents targets increased interest of medical practitioners to use chemotherapy for clinical activity in patients with molecular biomarkers in early detection, metastatic colorectal cancer. The goal in the diagnosis and in the prediction of therapeutic future will be to predict which specific treatment efficacy for clinical outcomes, chemotherapy and targeted agent combination academic and research institutions. will most likely benefit individual patients. Pharmaceuticals have increased their efforts to Personalized therapy for each patient is an develop novel molecular biomarkers for several important goal for improving the outcome of human diseases, including cancer. The patients with colorectal adenocarcinoma and identification of molecular biomarkers also includes the intention to maximize efficacy and enables the development of a new generation of minimize toxicity of chemotherapeutic agents. diagnostic products and to integrate diagnostics Clinical trials driven by molecular targets and and therapeutics. Identification and agents directed against colorectal understanding of these carcinogenic gene adenocarcinoma understand the conflicting data alterations is the base upon, which we can on utility of markers (Hamilton 2008; Iqbal and overcome drug resistance and develop novel Lenz 2004). Cytochrome c is primarily known for treatment approaches understanding of its function in the mitochondria as a key pharmacogenomics of pancreatic cancer participant in the life-supporting function of ATP treatment (Labourier and Winkler 2008; Manne synthesis and the release of cytochrome c and

Genomics: New aspect of cancer research

cytochrome-c-mediated apoptosis are controlled A reliable and useful clinical biomarker must by multiple layers of regulation. Its role in come from a readily attainable source, such as canonical intrinsic apoptosis, cytochrome c blood or urine and have sufficient sensitivity to amplifies signals that are generated by other correctly identify affected individuals. Also they apoptotic pathways and participates in certain are sufficient specificity to avoid incorrect non-apoptotic functions (Gao et al., 2005b; labeling of unaffected persons and result in a Shoshan-Barmatz et al., 2006; Ow et al., 2008). notable benefit for the patient through E3 ubiquitin ligases are a large family of intervention, such as survival or life quality proteins, which are engaged in the regulation of improvement. Genomics research have the turnover and activity of many target proteins. revolutionised cancer research in recent years Ubiquitin-proteasomal degradation pathway as high-throughput technologies can now be plays a critical role in protein degradation and used to identify sets of genes potentially related regulates a wide variety of cellular functions. with different processes in cancer. Also, This is highly conserved post-translational managing all genetic data and organising it into modification of proteolytic processes is mainly useful datasets is still a challenge in the carried out by substrate-specific E3 ligases. The bioinformatics field. Finding relationships growing understanding of metabolomics in between the molecular and genomic information cancer research play important role in cancer and the clinical information available, within the development and progression. This lead to the medical informatics domain and is currently development of a novel class of anticancer driving the development of translational research drugs targeting specific E3 ubiquitin ligases, as in biomedicine (Kohn et al., 2007; Stevens et al., well as the development of sensitive biomarkers 2003; Boyce and Kohn 2005; Kohn et al., 2003; for cancer treatment, diagnosis, and prognosis Simpkins et al., 2005). (Lakshmanan et al., 2008; Sun 2006; Newton and Vucic 2007; Pray et al., 2002). 8.8 Cancer informatics Bioinformatics operations are challenged to build 8.7 Bioinformatics approach data processing and delivery infrastructure, Bioinformatics is a rapidly emerging field of which provides reliable access and enables data biomedical and cancer research. A large-scale integration. Generated data must be processed genomic and postgenomic data can easily and stored such that relationships to external analysed by the help of computational science. data sources can be presented. Consistency Clinical informatics has long developed and comparability across data sets requires methodologies to improve biomedical research annotation with controlled vocabularies. and clinical care by integrating experimental and Metadata standards for data represent are used clinical information systems (Kim 2002; Kuo to access to the processed data should be 2003; Yang et al., 2008; Molidor et al., 2003). supported to ensure the maximum possible Now days, genome-wide detection of alternative value is extracted (Covitz et al., 2003; Gao et al., splicing based on Expressed Sequence Tag 2006). The development of cancer informatics (EST) sequence alignments with mRNA and techniques for oncogenomic analyses such as genomic sequences has dramatically expanded array comparative genomic hybridization, the understanding of the role of alternative messenger RNA expression arrays and splicing in functional regulation of cancer. mutational screens have come to the fore in Alternative splicing database schema design, it modern cancer research. These techniques are is possible to query genome-wide for alternative able to highlight panels of genes that are altered splicing patterns that are specific to particular in cancer (Bartlett 2001; Furney et al., 2008; tissues, disease states, gender or Jiang, et al., 2004). Advances in high-throughput developmental stages of cancer. EST technologies such as DNA microarrays have alignments can be used to estimate exon made it possible to simultaneously measure the inclusion or exclusion level of alternatively expression levels of thousands of genes and spliced exons and evolutionary changes for proteins. This has resulted in large amounts of various species can be inferred from exon biological data requiring analysis and inclusion level (Kim and Lee 2008; Hui et al., interpretation. The applications of functional 2004; Sugnet et al., 2004; Wang et al., 2003). genomics, proteomics and informatics to cancer Proteomics technologies are now being research have yielded a tremendous amount of advanced for the purpose of identification and information, which is growing all the time. This validation of new disease biomarkers in cancer. information is available publicly on the internet

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and ranges from general information about bicolor root hairs. J Biol Chem 283(6), different cancers from a patient or clinical 3231-3247. viewpoint, through to databases suitable for [4] Baylin SB, Chen WY. ( 2005 ) Aberrant gene cancer researchers (Devarajan 2008; Mejía-Roa silencing in tumor progression: et al., 2008; Brunet et al., 2004; Albertella 2001; implications for control of cancer. Cold Bader and Theofanos 2003). Spring Harb Symp Quant Biol. 70, 427-33. 9. Conclusion [5] Bartlett J. ( 2001 ) Technology evaluation: Genomics helped in the evolution of commercial SAGE, Genzyme molecular oncology. applications of single molecule DNA, RNA and Curr Opin Mol Ther. 3(1), 85-96. protein analysis. The various technologies [6] Begent RH ( 2007 ) Interpretation of extraction of high grade DNA from complex treatment results with biological agents: samples, tagging, microfluidics and genomic is there a need for a new methodology? mapping, addressing high value unmet needs in J BUON 12 Suppl 1, S53-S8. bio-security, human diagnostics, and food and [7] Bertucci F, Birnbaum D. ( 2008 ) Reasons drug contaminant monitoring. Genomics- for breast cancer heterogeneity. J Biol . mapping technologies are capable of identifying 7(2), 6. and quantitating individual molecules of DNA, [8] Beyer A, Bandyopadhyay S, Ideker T RNA and proteins in a complex sample. The (2007) Integrating physical and genetic human genome project is the biggest project maps: from genomes to interaction undertaken to date but there are many research networks. Nat Rev Genet 8(9), 699-710. projects around the world trying to map the gene [9] Bottcher C, Centeno D, Freitag J, Hofgen sequences of other organisms. This genomic R, Kohl K, Kopka J, Kroymann J, Matros mapping enables to develop new preventative A, Mock HP, Neumann S, Pfalz M, von and therapeutic approaches to the treatment of Roepenack-Lahaye E, Schauer N, disease and understand the mechanics of cell Trenkamp S, Zubriggen M, Fernie AR biology. Genomics is generating a lot of (2008 ) Teaching (and learning from) excitement not only in the scientific research metabolomics: the 2006 PlantMetaNet institutes and pharmaceutical companies but ETNA Metabolomics Research School. also in the financial and insurance worlds. Physiol Plant 132(2), 136-149. Universal reagent sets are used and no target [10] Bottero D, Gaillard ME, Fingermann M, amplification or culture is required. DNA Weltman G, Fernandez J, Sisti F, detection using these technologies provides Graieb A, Roberts R, Rico O, Rios G, genomic species identification, while quantitation Regueira M, Binsztein N, Hozbor D of RNAs and proteins can be used to track (2007 ) Pulsed-field gel electrophoresis, expression, within a highly mutiplexable assay pertactin, pertussis toxin S1 subunit format. Genomics strategies include high- polymorphisms, and surfaceome performance DNA sequencing that could analysis of vaccine and clinical dramatically reduce the cost of DNA sequencing Bordetella pertussis strains. Clin for research, drug development, and diagnostic Vaccine Immunol 14(11), 1490-1498. applications. [11] Boyce EA, Kohn EC. ( 2005 ) Ovarian cancer in the proteomics era: diagnosis, 10. References prognosis, and therapeutics targets. Int [1] Albertella MR. ( 2001 ) Cancer and the web. J Gynecol Cancer. 15 Suppl 3, 266-73. Comp Funct Genomics 2(1), 35-43. [12] Breyer MD, Tchekneva E, Qi Z, Takahashi [2] Bader JL, Theofanos MF. ( 2003 ) Searching T, Fogo AB, Harris RC ( 2007 ) for cancer information on the internet: Examining diabetic nephropathy through analyzing natural language search the lens of mouse genetics. Curr Diab queries. J Med Internet Res . 5(4), e31. Rep 7(6), 459-466. [3] Baerson SR, Dayan FE, Rimando AM, [13] Brinkhoff T, Giebel HA, Simon M ( 2008 ) Nanayakkara NP, Liu CJ, Schroder J, Diversity, ecology, and genomics of the Fishbein M, Pan Z, Kagan IA, Pratt LH, Roseobacter clade: a short overview. Cordonnier-Pratt MM, Duke SO ( 2008 ) Arch Microbiol s00203-008-0353y. A functional genomics investigation of [14] Brunet JP, Tamayo P, Golub TR, Mesirov allelochemical biosynthesis in Sorghum JP. ( 2004 ) Metagenes and molecular pattern discovery using matrix

Genomics: New aspect of cancer research

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