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Balagurunathan, K.

Publications and source records attributed to Balagurunathan, K..

2 recordsLinked to original sources

A graph-based algorithm for RNA-seq data normalization

The use of RNA-sequencing has garnered much attention in the recent years for characterizing and understanding various biological systems. However, it remains a major challenge to gain insights from a large number of RNA-seq experiments collectively, due to the normalization problem. Current normalization methods are based on assumptions that fail to hold when RNA-seq profiles become more abundant and heterogeneous. We present a normalization procedure that does not rely on these assumptions, or on prior knowledge about the reference transcripts in those conditions. This algorithm is based on a graph constructed from intrinsic correlations among RNA-seq transcripts and seeks to identify a set of densely connected vertices as references. Application of this algorithm on our benchmark data showed that it can recover the reference transcripts with high precision, thus resulting in high-quality normalization. As demonstrated on a real data set, this algorithm gives good results and is efficient enough to be applicable to real-life data.\n\n2012 ACM Subject ClassificationApplied computing [->] Computational transcriptomics, Applied computing [->] Bioinformatics\n\nDigital Object Identifier10.4230/LIPIcs.WABI.2018.xxx\n\nFundingThis material was based on research supported by the National Heart, Lung, and Blood Institute (NHLBI)-NIH sponsored Programs of Excellence in Glycosciences [grant number HL107152 to B.K.], and partially by NSF [CAREER grant 1350344 to M.M.]. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon.

bioinformatics

Click-xylosides overcome neurotoxic effects of reactive astrocytes and promote neuronal growth in a cell culture model of brain injury

Astrocytes, upon activation in response to brain injury, play a critical role in protecting neurons by limiting inflammation through the excessive secretion of many soluble factors, such as, chondroitin sulfate proteoglycans (CSPGs). Unfortunately, excessive CSPGs paradoxically prohibit neuronal recovery and growth, and eventually constitute a scar tissue. Many studies have attempted to overcome this barrier through various molecular approaches including the removal of inhibitory CSPGs by applying chondroitinase enzymes. In this study, we examined whether click-xylosides, which serve as primers of glycosaminoglycan (GAG) biosynthesis, can compete with endogenous inhibitory CSPGs for GAG assembly by serving as decoy molecules and thereby potentially reverse reactive astrocyte mediated neuronal growth inhibition. We investigated the axonal growth of hippocampal neurons in the presence of xyloside treated and untreated reactive astrocyte-conditioned media as a model recapitulating brain injury. Click-xylosides were found to interfere with the GAG biosynthetic machinery in astrocytes and reduced the amount of secreted inhibitory CSPGs by competing with endogenous assembly sites. The extent of underglycosylation was directly related to the outgrowth of hippocampal neurons. Overall, this study suggests that click-xylosides are promising therapeutic agents to treat CNS injuries and warrants further in vivo investigations.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC=\"FIGDIR/small/286450v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (24K):\norg.highwire.dtl.DTLVardef@185db74org.highwire.dtl.DTLVardef@10abd40org.highwire.dtl.DTLVardef@eecadorg.highwire.dtl.DTLVardef@1d48112_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience