Strand Life science Pvt. Ltd

Hebbal, India

Strand Life science Pvt. Ltd

Hebbal, India
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PubMed | Special Counsel, Thomas College, InvitroCue Pte Ltd, Independent Consultant & Researcher and 3 more.
Type: Journal Article | Journal: Pharmacogenomics | Year: 2015

We release the Janssen Toxicogenomics database. This rat liver gene-expression database was generated using Codelink microarrays, and has been used over the past years within Janssen to derive signatures for multiple end points and to classify proprietary compounds.The release consists of gene-expression responses to 124 compounds, selected to give a broad coverage of liver-active compounds. A selection of the compounds were also analyzed on Affymetrix microarrays.The release includes results of an in-house reannotation pipeline to Entrez gene annotations, to classify probes into different confidence classes. High confidence unambiguously annotated probes were used to create gene-level data which served as starting point for cross-platform comparisons. Connectivity map-based similarity methods show excellent agreement between Codelink and Affymetrix runs of the same samples. We also compared our dataset with the Japanese Toxicogenomics Project and observed reasonable agreement, especially for compounds with stronger gene signatures. We describe an R-package containing the gene-level data and show how it can be used for expression-based similarity searches.Comparing the same biological samples run on the Affymetrix and the Codelink platform, good correspondence is observed using connectivity mapping approaches. As expected, this correspondence is smaller when the data are compared with an independent dataset such as TG-GATE. We hope that this collection of gene-expression profiles will be incorporated in toxicogenomics pipelines of users.

PubMed | Medgenome Labs, Singapore Eye Research Institute, Narayana Nethralaya, GROW Research Laboratory and Strand Life science Pvt. Ltd.
Type: | Journal: BioMed research international | Year: 2015

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.

Neely G.G.,Austrian Academy of Sciences | Neely G.G.,Garvan Institute of Medical Research | Hess A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Costigan M.,Harvard University | And 39 more authors.
Cell | Year: 2010

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing. © 2010 Elsevier Inc.

Gollapalli K.,Indian Institute of Technology Bombay | Ray S.,Indian Institute of Technology Bombay | Srivastava R.,Indian Institute of Technology Bombay | Renu D.,Strand Life science Pvt. Ltd. | And 6 more authors.
Proteomics | Year: 2012

Glioblastoma multiforme (GBM) or grade IV astrocytoma is the most common and lethal adult malignant brain tumor. The present study was conducted to investigate the alterations in the serum proteome in GBM patients compared to healthy controls. Comparative proteomic analysis was performed employing classical 2DE and 2D-DIGE combined with MALDI TOF/TOF MS and results were further validated through Western blotting and immunoturbidimetric assay. Comparison of the serum proteome of GBM and healthy subjects revealed 55 differentially expressed and statistically significant (p <0.05) protein spots. Among the identified proteins, haptoglobin, plasminogen precursor, apolipoprotein A-1 and M, and transthyretin are very significant due to their functional consequences in glioma tumor growth and migration, and could further be studied as glioma biomarkers and grade-specific protein signatures. Analysis of the lipoprotein pattern indicated elevated serum levels of cholesterol, triacylglycerol, and low-density lipoproteins in GBM patients. Functional pathway analysis was performed using multiple software including ingenuity pathway analysis (IPA), protein analysis through evolutionary relationships (PANTHER), database for annotation, visualization and integrated discovery (DAVID), and GeneSpring to investigate the biological context of the identified proteins, which revealed the association of candidate proteins in a few essential physiological pathways such as intrinsic prothrombin activation pathway, plasminogen activating cascade, coagulation system, glioma invasiveness signaling, and PI3K signaling in B lymphocytes. A subset of the differentially expressed proteins was applied to build statistical sample class prediction models for discrimination of GBM patients and healthy controls employing partial least squares discriminant analysis (PLS-DA) and other machine learning methods such as support vector machine (SVM), Decision Tree and Naïve Bayes, and excellent discrimination between GBM and control groups was accomplished. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ray S.,Indian Institute of Technology Bombay | Renu D.,Strand Life science Pvt. Ltd. | Srivastava R.,Indian Institute of Technology Bombay | Gollapalli K.,Indian Institute of Technology Bombay | And 11 more authors.
PLoS ONE | Year: 2012

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases. © 2012 2012 Ray et al.

Patel S.,San Diego State University | Patel S.,Strand Life science Pvt. Ltd.
VirusDisease | Year: 2016

Ebola virus, a member of the family Filoviridae has caused immense morbidity and mortality in recent times, especially in West Africa. The infection characterized by chills, fever, diarrhea, and myalgia can progress to hemorrhage and death. Hence, it is a high priority area to better understand its biology in order to expedite vaccine development pipelines. In this regard, this study analyzes the domains in RNA polymerase of fifteen publicly-available Ebola isolates belonging to three strains (Zaire, Sudan and Reston). The protein FASTA sequences of the isolates belonging Zaire, Sudan and Reston strains were extracted from UniProt database and submitted to the interactive web tool SMART for the polymerase domain profiles. Subsequent in silico investigation furnished interesting results that sure can contribute to the understanding of Ebola pathogenesis. The key findings and patterns have been presented, and based on them hypotheses have been formulated for further empirical validation. © 2016 Indian Virological Society

Awasthy D.,Astrazeneca | Awasthy D.,Biocon | Ambady A.,Astrazeneca | Ambady A.,Strand Life science Pvt. Ltd | And 5 more authors.
Gene | Year: 2014

Most bacteria are able to generate sufficient amounts of ATP from substrate level phosphorylation, thus rendering the respiratory oxidative phosphorylation non-critical. In mycobacteria, including Mycobacterium tuberculosis, ATP generation by oxidative phosphorylation is an essential process. Of the two types of NADH dehydrogenases (type I and type II), the type II NADH dehydrogenase (Ndh) which is inhibited by phenothiazines has been thought to be essential. In M. tuberculosis there are two Ndh isozymes (Ndh and NdhA) coded by ndh and ndhA genes respectively. Ndh and NdhA share a high degree of amino acid similarity. Both the enzymes have been shown to be enzymatically active and are inhibited by phenothiazines, suggesting a functional similarity between the two. We attempted gene knockout of ndh and ndhA genes in wild type and merodiploid backgrounds. It was found that ndh gene cannot be inactivated in a wild type background, though it was possible to do so when an additional copy of ndh was provided. This showed that in spite of its apparent functional equivalence, NdhA cannot complement the loss of Ndh in M. tuberculosis. We also showed that NdhA is not essential in M. tuberculosis as the ndhA gene could be deleted in a wild type strain of M. tuberculosis without causing any adverse effects in vitro. RT-PCR analysis of in vitro grown M. tuberculosis showed that ndhA gene is actively transcribed. This study suggests that despite being biochemically similar, Ndh and NdhA play different roles in the physiology of M. tuberculosis. © 2014 Elsevier B.V.

Morayya S.,Biocon | Awasthy D.,Strand Life science Pvt. Ltd. | Yadav R.,Astrazeneca | Ambady A.,Biocon | Sharma U.,GangaGen Biotechnologies Pvt. Ltd
Gene | Year: 2015

Glutamate racemase (MurI) converts l-glutamate into d-glutamate which is an essential component of peptidoglycan in bacteria. The gene encoding glutamate racemase, murI has been shown to be essential for the growth of a number of bacterial species including Escherichia coli. However, in some Gram-positive species d-amino acid transaminase (Dat) can also convert l-glutamate into d-glutamate thus rendering MurI non-essential for growth. In a recent study the murI gene of Mycobacterium tuberculosis was shown to be non-essential. As d-glutamate is an essential component of peptidoglycan of M. tuberculosis, either Dat or MurI has to be essential for its survival. Since, a Dat encoding gene has not been reported in M. tuberculosis genome sequence, the reported non-essentiality of murI was unexplainable. In order to resolve this dilemma we tried to knockout murI in the presence of single and two copies of murI, in wild type and merodiploid strains respectively. It was found that murI could not be inactivated in the wild type background indicating that it could be an essential gene. Also, inactivation of murI could not be achieved in the presence of externally supplied d-glutamate in 7H9 medium suggesting that M. tuberculosis is unable to take up d-glutamate under the conditions tested. However we could generate murI knockout strains at high frequency when two copies of the gene were present indicating that at least one murI gene is required for cellular viability. The essential nature of MurI in M. tuberculosis H37Rv suggests that it could be a potential drug target. © 2014 Elsevier B.V.

PubMed | Agilent Technologies, SAP, University of Konstanz, University of Ulm and Strand Life science Pvt. Ltd.
Type: Journal Article | Journal: Journal of molecular psychiatry | Year: 2015

Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD.Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA).Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%.This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology.

PubMed | Grant Government Medical College and Sir JJ Group of Hospitals, Hinduja National Hospital &Medical Research Center, P.A. College, Medical College Hospital Kolkata and 4 more.
Type: | Journal: Scientific reports | Year: 2016

In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

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