01374nas a2200145 4500008004100000245010200041210006900143260000800212300001200220490000600232520081500238100002601053700002101079856012801100 2015 eng d00aData in support of large scale comparative codon usage analysis in leishmania and trypanosomatids0 aData in support of large scale comparative codon usage analysis  cJUN a269-2720 v43 a

This data article contains data related to the article “Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions” 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.

1 aSubramanian, Abhishek1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/data-support-large-scale-comparative-codon-usage-analysis-leishmania-and-trypanosomatids02853nas a2200169 4500008004100000022001400041245007700055210006900132260009100201300002900292490000700321520217900328100002602507700001902533700002102552856011002573 2015 eng d a1932-620300aDissecting leishmania infantum energy metabolism - a systems perspective0 aDissecting leishmania infantum energy metabolism a systems persp a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcSEP aArticle Number: e01379760 v103 a

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.

1 aSubramanian, Abhishek1 aJhawar, Jitesh1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/dissecting-leishmania-infantum-energy-metabolism-systems-perspective-102307nas a2200217 4500008004100000022001400041245011500055210006900170260008800239300001200327490000700339520140300346653001701749653002001766653003101786653005701817653004301874100002601917700002101943856012501964 2015 eng d a0218-339000aDynamics of gli regulation and a strategy to control cancerous situation: hedgehog signaling pathway revisited0 aDynamics of gli regulation and a strategy to control cancerous s a5 TOH TUCK LINK, SINGAPORE 596224, SINGAPOREbWORLD SCIENTIFIC PUBL CO PTE LTDcDEC a681-7190 v233 a

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.

10aGLI Dynamics10aGraded Response10aHedgehog Signaling Pathway10aLigand-Dependent and -Independent Pathway Activation10aUltrasensitive and Irreversible Switch1 aSubramanian, Abhishek1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/dynamics-gli-regulation-and-strategy-control-cancerous-situation-hedgehog-signaling-0