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Applications of Bioinformatics Tools in Stem Cell Research Polani B.Ramesh Babu et al. / Journal of Pharmacy Research 2012,5(9),4863-4866 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Applications of Bioinformatics Tools in Stem Cell Research: An Update Polani B.Ramesh Babu and P.Krishnamoorthy Department of Bioinformatics, School of Bio-Engineering. Bharath Institute of Science and Technology, Bharath University. Chennai. India. Received on:12-06-2012; Revised on: 17-07-2012; Accepted on:26-08-2012 ABSTRACT Bioinformatics originated as a cross-disciplinary field as the need for computational solutions to research problems raised in biomedicine. Stem cell driven regenerative systems are highly complex and dynamic, consisting of large numbers of different cells expressing many molecules controlling their fates. Therefore, mathematical models and computational tools are necessary - both to aid the interpretation of experimental data and to simulate the behavior of stem cell systems based on hypothetical assumptions about their complex cellular or molecular composition. Many long-standing questions in stem cell research remain unsolved. In this review, we describe recent developments and advancements in bioinformatics tools applicable in stem cell research. Key words: Stem cells, Bioinformatics, Computation, Pluripotency INTRODUCTION Bioinformatics is the application of computer science and information tech- of equivalent human ES cells, have now opened new vistas for regenerative nology to the field of biology and medicine. This rapidly developing branch medicine. Induced pluripotent stem cells (iPS or iPSC) are produced by of biology is highly interdisciplinary using concepts and techniques from nuclear reprogramming technology and they resemble ES cells in key ele- informatics, statistics, mathematics, retrieval and analysis of data [1,2]. ments [14]; they possess the potentiality to differentiate into any type of Major research efforts in Bioinformatics with reference to Stem cells in- cell in the body. More importantly, the iPS platform has distinct advantage clude DNA/protein sequence alignment, gene finding, gene assembly, pro- over ES system in the sense that iPS-derived cells are autologous and there- tein structure alignment, protein structure prediction, prediction of gene fore the iPS-derived transplantation does not require immunosuppressive expression, protein–protein interactions, genome-wide association studies, therapy. In addition, iPS research obviates the political and ethical quan- the modeling for various diseases, drug design and drug discovery. dary associated with embryo destruction and ES research. This remarkable discovery of cellular plasticity has important medical implications. Software tools in bioinformatics range from simple command-line tools, to more complex graphical programs and standalone web-services [3]. The use Both ES cells and iPS cells receive a marked attention from scientists and of online/internet resources or graphical navigation software (i.e. web brows- clinicians for regenerative medicine because of their high proliferative and ers) for the Internet was developed and used on a widespread scale. Produc- differentiation capacities. Most recent application of human ES and PS tion of high throughput biological data in terms of ‘genomics’, ‘microarrays’ cells may, however, reside in their use as a tool in drug development, disease and ‘proteomics’ in Stem cell biology increased continually with a distinct modeling and new modes of therapy [15,16,17]. The ease with which they acceleration [4.5.6] . Recently various tools are used to creating models or can be grown in bulk and their differentiation controlled in vitro is of impor- viewing 3-D models for adult tissue/organ developments in regenerative tance for their widespread adoption by industry and their clinical efficacy. medicine [7,8,9]. Small molecules have already had a positive impact on several areas of stem cell biology, from maintenance of pluripotency [10], the promotion of single Stem cells are a class of undifferentiated cells that are able to differentiate cell survival and steering differentiation to involvement in reprogramming into specialized cell types. Commonly, stem cells come from embryos somatic cells. High-throughput technology has played an important role in formed during the blastocyst phase of embryological development (embry- identifying novel compounds, however to date there are few published onic stem cells) and adult tissue (adult stem cells)[7]. Both types are gener- examples of medicinal chemistry input in this area. ally characterized by their potency, or potential to differentiate into differ- ent cell types (such as skin, muscle, bone, etc.)[7,10]. The Pluripotent cells The field of stem-cell biology has been catapulted forward by the startling (PS) have the ability to differentiate into almost all cell types, examples development of reprogramming technology [14,18] and somatic cell nuclear include embryonic stem cells and cells that are derived from the mesoderm, transfer or therapeutic cloning has provided great hope for stem cell-based endoderm, and ectoderm germ layers that are formed in the beginning stages therapies (Table 1). Recent breakthrough studies using a combination of of embryonic stem cell differentiation [11,12,13]. four factors to reprogram human somatic cells into PS cells without using embryos or eggs have led to an important revolution in stem cell research The discovery of embryonic stem (ES) cells came from the conjunction of [14,18]. Comparative analysis of human iPS cells and human ES cells using studies in human pathology, mouse genetics, early mouse embryo develop- assays for morphology, cell surface marker expression, gene expression ment, cell surface immunology and tissue culture [7,11]. They have not profiling, epigenetic status, and differentiation potential have revealed a only revolutionized experimental mammalian genetics but, with the advent remarkable degree of similarity between these two pluripotent stem cell types. These advances in reprogramming will enable the creation of patient- *Corresponding author. specific stem cell lines to study various disease mechanisms. Furthermore, Polani B.Ramesh Babu this reprogramming system provides great potential to design customized Department of Bioinformatics, patient-specific stem cell therapies with economic feasibility. Disease-spe- School of Bio-Engineering. cific human ES cells were the first to provide a useful source for studying Bharath Institute of Science and Technolgy, certain disease states. The recent demonstration that human somatic cells, Bharath University. Chennai. India. derived from readily accessible tissue such as skin or blood, can be con- Journal of Pharmacy Research Vol.5 Issue 9.September 2012 4863-4866 Polani B.Ramesh Babu et al. / Journal of Pharmacy Research 2012,5(9),4863-4866 verted to embryonic-like induced pluripotent stem cells (hiPSCs) has opened FGF, BMP, Insulin, Notch and LIF), and epigenetic regulators as well as new perspectives for modeling and understanding a larger number of human some other relevant genes/proteins, such as proteins involved in nuclear pathologies. import/export. Table 1 : Therapeutic Potential of Stem cells in Regenerative Medicine Table 2 : List of Bioinformatics tools used in Stem Cell Research. Name of the Description of the tool Application in stem cell research Disease Stem Cell Potential Bioinformatic tools Heart disease Adult bone marrow stem cells injected into heart arteries are believed to improve cardiac function in victims of heart attack or heart failure. hESCreg Online resource for European A global registry providing comprehensive Leukemia and other In various studies leukemia patients treated with stem cells from human embryonic stem cell information on available hESC lines including cancers bone marrow and umbilical cord emerged free of disease; donor blood registry their, derivation culture, genetics, potency stem cells have also reduced non-Hodgkin’s lymphoma, and pancreatic and procurement/ethical provenance. and ovarian cancer in some patients Rheumatoid Adult stem cells may be helpful in jump-starting repair of eroded CellFinder A stem cell navigation tool Provides linkage of individual cell lines or arthritis cartilage.In human trials, joint pain lessened temporarily after donor groups of cells to genetic or functional stem cell therapy in some patients,.and some then responded better to characteristics from sources outside of standard drug therapies hESCreg, e.g. expression profiles for Parkinson’s Since fetal tissue implants had mixed success in reducing neurological differentiated or pluripotent cells disease symptoms, some researchers say the best hope is that a patient’s own Genomatix Computational Search tool Suggests novel transcription factors for neural stem cells may eventually be coaxed to mature into the dopamine- and database stemness producing cells needed to treat the disease PluriNetWork An Electronic representation A large network of interaction and regulation Type I diabetes Basic research is focused on understanding how embryonic stem cells of the Network and data links between genes/proteins involved in might be trained to become the type of pancreatic islet cells that secrete repository pluripotency needed insulin. Recent developments using proteins to spur cell StemBase A simple web-interface The largest online repositories for human and differentiation may speed progress. mouse stem cell gene expression data Stem cell genome- Computational
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