@article {43043, title = {Data in support of large scale comparative codon usage analysis in leishmania and trypanosomatids}, journal = {Data Brief}, volume = {4}, year = {2015}, month = {JUN}, pages = {269-272}, type = {Article}, abstract = {

This data article contains data related to the article {\textquotedblleft}Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions{\textquotedblright} by Subramanian and Sarkar [1]. The data comprises of sequence-based measures that quantify the effect of codon usage across genomes. The data thus generated represents computed values of codon usage indices like relative synonymous codon usage (RSCU), effective number of codons (ENC), and codon adaptation index (CAI), a set of single copy orthologous genes common to the 13 Trypanosomatids, and comparisons of CAI between genes of different functions. This forms a basis of comparison to infer the causes and consequences of codon usage bias in Leishmania and other Trypanosomatids.

}, doi = {10.1016/j.dib.2015.06.003}, author = {Subramanian, Abhishek and Sarkar, Ram Rup} } @article { ISI:000361601100191, title = {Dissecting leishmania infantum energy metabolism - a systems perspective}, journal = {Plos One}, volume = {10}, number = {9}, year = {2015}, month = {SEP}, pages = {Article Number: e0137976}, publisher = {PUBLIC LIBRARY SCIENCE}, address = {1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA}, abstract = {

Leishmania infantum, causative agent of visceral leishmaniasis in humans, illustrates a complex lifecycle pertaining to two extreme environments, namely, the gut of the sandfly vector and human macrophages. Leishmania is capable of dynamically adapting and tactically switching between these critically hostile situations. The possible metabolic routes ventured by the parasite to achieve this exceptional adaptation to its varying environments are still poorly understood. In this study, we present an extensively reconstructed energy metabolism network of Leishmania infantum as an attempt to identify certain strategic metabolic routes preferred by the parasite to optimize its survival in such dynamic environments. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. To explore the diverse features of parasite metabolism the metabolic network was implemented and analyzed as a constraint-based model. Using a systems-based approach, we also put forth an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Further, the fate of important non-essential amino acids in L. infantum metabolism was investigated. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism and its optimal growth. Finally, through our in silico knockout analysis, we could identify possible therapeutic targets that provide experimentally testable hypotheses.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0137976}, author = {Subramanian, Abhishek and Jhawar, Jitesh and Sarkar, Ram Rup} } @article { ISI:000365700200007, title = {Dynamics of gli regulation and a strategy to control cancerous situation: hedgehog signaling pathway revisited}, journal = {Journal of Biological Systems}, volume = {23}, number = {4}, year = {2015}, month = {DEC}, pages = {681-719}, publisher = {WORLD SCIENTIFIC PUBL CO PTE LTD}, address = {5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE}, abstract = {

The hedgehog signaling cascade generates highly diverse, fine-tuned responses in response to the external stimulus by the sonic hedgehog (SHH) protein. This is required for the flawless functioning of the cell, its development, survival and proliferation; maintained through production of Glioma protein (GLI) and transcriptional activation of its target genes. Any change in the behavior of GLI response by ectopic expression of SHH or mutations in the core pathway components may cause serious consequences in the cell fate through rapid, uncontrolled and elevated production of GLI. Here, we present a simple but extensive computational model that considers the detailed reaction mechanisms involved in the hedgehog signal transduction and provides a detailed insight into regulation of GLI. For the first time, by explicit involvement of suppressor of fused (SUFU) and Hedgehog interacting protein (HHIP) reaction kinetics in the model, we try to demonstrate the vital importance of HHIP and SUFU in maintaining the graded response of GLI in response to SHH. By performing parameter variations, we capture the conversion of a graded response of GLI to an ultrasensitive switch under SUFU-deficient conditions that might predispose abnormal embryonic development and the irreversible switching response of GLI that corresponds to signal-independent pathway activation observed in cancers.

}, keywords = {GLI Dynamics, Graded Response, Hedgehog Signaling Pathway, Ligand-Dependent and -Independent Pathway Activation, Ultrasensitive and Irreversible Switch}, issn = {0218-3390}, doi = {10.1142/S0218339015500333}, author = {Subramanian, Abhishek and Sarkar, Ram Rup} }