Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeu... more Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeutics (i.e. kinase inhibitors). However, many fusion proteins involved in various cellular processes have not been studied for targeted therapeutics. This is because the lack of complete fusion protein sequences and their whole 3D structures has made it challenging to develop new therapeutic strategies. To fill these critical gaps, we developed a computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB is organized into four levels: 43K fusion protein sequences (14.7K in-frame fusion genes, Level 1), over 2300Â +Â 1267 fusion protein 3D structures (from 2300 recurrent and 266 manually curated in-frame fusion genes, Level 2), pLDDT score analysis for the 1267 fusion proteins from 266 manually curated fusion genes (Level 3), and virtual screening outcomes for 68 selected fusion proteins from 266 manually curated ...
Tumorigenic functions due to the formation of fusion genes were targeted for cancer therapeutics ... more Tumorigenic functions due to the formation of fusion genes were targeted for cancer therapeutics (i.e., kinase inhibitors). However, there are still many fusion proteins awaiting being targeted for therapeutics with multiple different mechanisms. Due to the lack of knowledge of the fusion protein sequence and 3D structure, there were not many studies available. To fill this gap, we developed a new computational pipeline and a resource of human fusion proteins, named FusionPDB available at https://compbio.uth.edu/FusionPDB. FusionPDB provides ~ 42K fusion protein sequences (of 16K in-frame fusion genes), 2300 + 1267 fusion protein 3D structures (of 2300 recurrent in-frame fusion genes and 266 manually curated in-frame fusion genes), and virtual screening results of 1267 fusion proteins. FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until covering all human fusion prote...
Summary Even though there were many tool developments of fusion gene prediction from NGS data, to... more Summary Even though there were many tool developments of fusion gene prediction from NGS data, too many false positives are still an issue. Wise use of the genomic features around the fusion gene breakpoints will be helpful to identify reliable fusion genes efficiently. For this aim, we developed FusionAI, a deep learning pipeline predicting human fusion gene breakpoints from DNA sequence. FusionAI is freely available via https://compbio.uth.edu/FusionGDB2/FusionAI. For complete details on the use and execution of this protocol, please refer to Kim et al. (2021b).
Mango is one of the important perennial fruit crops that exhibits bienniality and results in high... more Mango is one of the important perennial fruit crops that exhibits bienniality and results in high economic loss. The molecular mechanisms involved in the bienniality behavior of mango are yet to be fully explored. In this study, an attempt was made to identify putative genes and amino acid residues playing an important role in biennial rhythm in mango through comparative genomics approach. Here, the reported genes responsible for bienniality in Arabidopsis and apple were used to identify the corresponding orthologs in mango. The phylogenetic analysis was also carried out to understand the evolutionary relationships among the bienniality related proteins of mango, Arabidopsis and apple. Further, the amino acid residues conserved in the protein products of the candidate genes in mango were identified by both sequence and structure alignment. From both the alignments, arginine and glycine were found conserved in the candidate bienniality proteins of mango that indicates the possible in...
Transcriptome expression reflects genetic response in diverse conditions. In this study, RNA sequ... more Transcriptome expression reflects genetic response in diverse conditions. In this study, RNA sequencing was utilized to profile multiple tissues such as liver, breast, caecum, and gizzard of Korean commercial chicken raised in Korea and Kyrgyzstan. We analyzed ten samples per tissue from each location to identify candidate genes which are involved in the adaptation of Korean commercial chicken to Kyrgyzstan. At false discovery rate (FDR) < 0.05 and fold change (FC) > 2, we found 315, 196, 167 and 198 genes in liver, breast, cecum, and gizzard respectively as differentially expressed between the two locations. GO enrichment analysis showed that these genes were highly enriched for cellular and metabolic processes, catalytic activity, and biological regulations. Similarly, KEGG pathways analysis indicated metabolic, PPAR signaling, FoxO, glycolysis/gluconeogenesis, biosynthesis, MAPK signaling, CAMs, citrate cycles pathways were differentially enriched. Enriched genes like TSKU,...
Heat stress (HS) negatively impacts pig production and swine health. Therefore, to understand the... more Heat stress (HS) negatively impacts pig production and swine health. Therefore, to understand the genetic and metabolic responses of pigs to HS, we used RNA-Seq and high resolution magic angle spinning (HR-MAS) NMR analyses to compare the transcriptomes and metabolomes of Duroc pigs (n = 6, 3 barrows and 3 gilts) exposed to heat stress (33 °C and 60% RH) with a control group (25 °C and 60% RH). HS resulted in the differential expression of 552 (236 up, 316 down) and 879 (540 up, 339 down) genes and significant enrichment of 30 and 31 plasma metabolites in female and male pigs, respectively. Apoptosis, response to heat, Toll-like receptor signaling and oxidative stress were enriched among the up-regulated genes, while negative regulation of the immune response, ATP synthesis and the ribosomal pathway were enriched among down-regulated genes. Twelve and ten metabolic pathways were found to be enriched (among them, four metabolic pathways, including arginine and proline metabolism, and...
ecotypes. This study provides information on the HS response of chickens, adapted to two differen... more ecotypes. This study provides information on the HS response of chickens, adapted to two different agro climatic environments, extending our understanding of the mechanisms of HS response and the effect of adaptation in counteracting HS.
International Journal for Computational Biology, 2015
A Drug designing is a process in which new leads (potential drugs) are discovered which have ther... more A Drug designing is a process in which new leads (potential drugs) are discovered which have therapeutic benefits in diseased condition. With development of various computational tools and availability of databases (having information about 3D structure of various molecules) discovery of drugs became comparatively, a faster process. The two major drug development methods are structure based drug designing and ligand based drug designing. Structure based methods try to make predictions based on three dimensional structure of the target molecules. The major approach of structure based drug designing is Molecular docking, a method based on several sampling algorithms and scoring functions. Docking can be performed in several ways depending upon whether ligand and receptors are rigid or flexible. Hotspot grafting, is another method of drug designing. It is preferred when the structure of a native binding protein and target protein complex is available and the hotspots on the interface are known. In absence of information of three Dimensional structure of target molecule, Ligand based methods are used. Two common methods used in ligand based drug designing are Pharmacophore modelling and QSAR. Pharmacophore modelling explains only essential features of an active ligand whereas QSAR model determines effect of certain property on activity of ligand. Fragment based drug designing is a de novo approach of building new lead compounds using fragments within the active site of the protein. All the candidate leads obtained by various drug designing method need to satisfy ADMET properties for its development as a drug. Insilico ADMET prediction tools have made ADMET profiling an easier and faster process. In this review, various softwares available for drug designing and ADMET property predictions have also been listed.
International Journal for Computational Biology, 2014
Repeat of amino acids in a protein sequence has clinical and functional importance. Database of P... more Repeat of amino acids in a protein sequence has clinical and functional importance. Database of Perfect Amino Acid Repeat (DPAAR) is a kind of relational as well as flat file database which is created by the comprehensive analysis of 5,42,782 protein sequences of Swiss-Prot database (released on 19 th March,2014) to know the association between repeated sequence and disease. It provides the search engine for rapid access of a particular repeated amino acid, or particular swissprot ID, or particular length of repeated amino acids in a protein sequence. It also provides the flat files for single, oligo, and tandem repeated sequence information to get the complete informaton about concerned amino acids repeat. It consists of the tables of repeated sequence and its associated disease in human being.
The microbial composition in the cecum of pig influences host health, immunity, nutrient digestio... more The microbial composition in the cecum of pig influences host health, immunity, nutrient digestion, and feeding requirements significantly. Advancements in metagenome sequencing technologies such as 16S rRNAs have made it possible to explore cecum microbial population. In this study, we performed a comparative analysis of cecum microbiota of crossbred Korean native pigs at two different growth stages (stage L = 10 weeks, and stage LD = 26 weeks) using 16S rRNA sequencing technology. Our results revealed remarkable differences in microbial composition, α and β diversity, and differential abundance between the two stages. Phylum composition analysis with respect to SILVA132 database showed Firmicutes to be present at 51.87% and 48.76% in stages L and LD, respectively. Similarly, Bacteroidetes were present at 37.28% and 45.98% in L and LD, respectively. The genera Prevotella, Anaerovibrio, Succinivibrio, Megasphaera were differentially enriched in stage L, whereas Clostridium, Terrispo...
Journal of Biomedical Translational Research, 2018
Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat... more Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP × Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (|log2FC| > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.
Positive results of many Trials have incorporated concurrent and sequential chemo radiotherapy in... more Positive results of many Trials have incorporated concurrent and sequential chemo radiotherapy in treatment of inoperable carcinoma esophagus. But concurrent chemo radiation therapy is similar to that achieved by surgery alone. The main plea of concurrent chemoradiation in esophageal cancers is early regression and palliation of dysphagia for long time. The aim of this study to analyse the modalities of treatment available for palliation of dysphagia in carcinoma esophagus and determine the most effective option among them. Materials and Methods: Between September 2011 to December 2013,50 patients of esophageal cancers were treated in our institute, 25 patients in sequential and 25 in concurrent chemo radiotherapy arm. Swallowing function was assessed in these patients by the use of a swallowing-function scoring system. Results: Assessment of response in two arms were done for grade of dysphagia palliation, Complete Response at 6 months and toxicity. Dysphagia scores improved in 88% in study arm and 64% in control arm. In study arm 28% male and 52% female patients, while in control arm 40 % male and 28% female patients presented with CR in primary tumor and mediastinal lymph node. There was statistical significant difference in toxicities of TLC and ANC between both arms. Grade 2 and 3 toxicities were 40% and 4% for TLC and were 28% and 0% for ANC in study and control arm respectively (p = 0.013 ,p=.014). This may be due to concurrent use of chemotherapy with radiation in study arm that also showed synergism for toxicity of TLC and ANC. Conclusion: Concurrent Chemo Radiotherapy is a more aggressive approach for dysphagia control, which is beneficial for those patients with good performance status .This approach is used as an alternative to stenting. This combination is more effective than neoadjuvant chemoradiation for improving dysphagia scores and QoL in inoperable esophageal cancers .
Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of... more Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of two oncogenes namely BCR and ABL with their aberrant expression. Autophosphorylation of BCR-ABL oncogenes results in proliferation of CML. The study deals with estimation of rate constant involved in each step of the cellular autophosphorylation process, which are consequently playing important roles in the proliferation of cancerous cells. Materials and Methods: A mathematical model was proposed for autophosphorylation of BCR-ABL oncogenes utilizing ordinary differential equations to enumerate the rate of change of each responsible system component. The major difficulty to model this process is the lack of experimental data, which are needed to estimate unknown model parameters. Initial concentration data of each substrate and product for BCR-ABL systems were collected from the reported literature. All parameters were optimized through time interval simulation using the fminsearch algorithm. Results: The rate of change versus time was estimated to indicate the role of each state variable that are crucial for the systems. The time wise change in concentration of substrate shows the convergence of each parameter in autophosphorylation process. Conclusions: The role of each constituent parameter and their relative time dependent variations in autophosphorylation process could be inferred.
Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on... more Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of-10.940 kcal/mol and Glide e-model score of-86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.
Interdisciplinary sciences, computational life sciences, Jan 16, 2016
Cereal grain bread wheat (T. aestivum) is an important source of food and belongs to Poaceae fami... more Cereal grain bread wheat (T. aestivum) is an important source of food and belongs to Poaceae family. Hypothetical proteins (HPs), i.e., proteins with unknown functions, share a substantial portion of wheat proteomes and play important roles in growth and physiology of plant system. Several functional annotations studies utilizing the protein sequences for characterization of role of individual protein in physiology of plant systems were being reported in recent past. In this study, an integrated pipeline of software/servers has been used for the identification and functional annotation of 124 unique HPs of T. aestivum considering available data in NCBI till date. All HPs were broadly annotated, out of which functions of 77 HPs were successfully assigned with high confidence level. Precisely functional annotation of remaining 47 HPs is also characterized with low confidence. Several latest versions of protein family databases, pathways information, genomics context methods and in sil...
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to ab... more Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc. In this study IL-6 pathways have been taken into consideration which induces JAK/STAT and MAPK pathways to decipher the CML progression stages. An attempt has been made to model these pathways with the help of ordinary differential equations (ODEs) and estimating unknown parameters through fminsearch optimization algorithm. Some of the specific component like STAT3, of the pathway has been analyzed in detail and their role in CML progression has been elucidated. The roles of STAT3 inhibitors into the treatment of CML have been thoroughly studied and optimum concentration of the inhibitors have been predicted.
Journal of biomolecular structure & dynamics, Jan 19, 2015
Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been p... more Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been proven as the prime cause of Chronic Myeloid Leukemia (CML). It has been established that tyrosine kinase domain of BCR-ABL protein is a potential therapeutic target for the treatment of CML. Imatinib is considered as a first generation drug that can inhibit the enzymatic action by inhibiting the ATP binding with BCR-ABL protein. Later on, insensitivity of CML cells towards Imatinib has been observed may be due to mutation in tyrosine kinase domain of the ABL receptor. Subsequently some other second generation drugs have also been reported viz. Baustinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib etc., which can able to combat against mutated domain of ABL tyrosine kinase protein. By taking into account of bioavailability and resistance developed, there is an utmost need to find some more inhibitors for the mutated ABL tyrosine kinase protein. For virtual screening, a dataset has been ge...
Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeu... more Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeutics (i.e. kinase inhibitors). However, many fusion proteins involved in various cellular processes have not been studied for targeted therapeutics. This is because the lack of complete fusion protein sequences and their whole 3D structures has made it challenging to develop new therapeutic strategies. To fill these critical gaps, we developed a computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB is organized into four levels: 43K fusion protein sequences (14.7K in-frame fusion genes, Level 1), over 2300Â +Â 1267 fusion protein 3D structures (from 2300 recurrent and 266 manually curated in-frame fusion genes, Level 2), pLDDT score analysis for the 1267 fusion proteins from 266 manually curated fusion genes (Level 3), and virtual screening outcomes for 68 selected fusion proteins from 266 manually curated ...
Tumorigenic functions due to the formation of fusion genes were targeted for cancer therapeutics ... more Tumorigenic functions due to the formation of fusion genes were targeted for cancer therapeutics (i.e., kinase inhibitors). However, there are still many fusion proteins awaiting being targeted for therapeutics with multiple different mechanisms. Due to the lack of knowledge of the fusion protein sequence and 3D structure, there were not many studies available. To fill this gap, we developed a new computational pipeline and a resource of human fusion proteins, named FusionPDB available at https://compbio.uth.edu/FusionPDB. FusionPDB provides ~ 42K fusion protein sequences (of 16K in-frame fusion genes), 2300 + 1267 fusion protein 3D structures (of 2300 recurrent in-frame fusion genes and 266 manually curated in-frame fusion genes), and virtual screening results of 1267 fusion proteins. FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until covering all human fusion prote...
Summary Even though there were many tool developments of fusion gene prediction from NGS data, to... more Summary Even though there were many tool developments of fusion gene prediction from NGS data, too many false positives are still an issue. Wise use of the genomic features around the fusion gene breakpoints will be helpful to identify reliable fusion genes efficiently. For this aim, we developed FusionAI, a deep learning pipeline predicting human fusion gene breakpoints from DNA sequence. FusionAI is freely available via https://compbio.uth.edu/FusionGDB2/FusionAI. For complete details on the use and execution of this protocol, please refer to Kim et al. (2021b).
Mango is one of the important perennial fruit crops that exhibits bienniality and results in high... more Mango is one of the important perennial fruit crops that exhibits bienniality and results in high economic loss. The molecular mechanisms involved in the bienniality behavior of mango are yet to be fully explored. In this study, an attempt was made to identify putative genes and amino acid residues playing an important role in biennial rhythm in mango through comparative genomics approach. Here, the reported genes responsible for bienniality in Arabidopsis and apple were used to identify the corresponding orthologs in mango. The phylogenetic analysis was also carried out to understand the evolutionary relationships among the bienniality related proteins of mango, Arabidopsis and apple. Further, the amino acid residues conserved in the protein products of the candidate genes in mango were identified by both sequence and structure alignment. From both the alignments, arginine and glycine were found conserved in the candidate bienniality proteins of mango that indicates the possible in...
Transcriptome expression reflects genetic response in diverse conditions. In this study, RNA sequ... more Transcriptome expression reflects genetic response in diverse conditions. In this study, RNA sequencing was utilized to profile multiple tissues such as liver, breast, caecum, and gizzard of Korean commercial chicken raised in Korea and Kyrgyzstan. We analyzed ten samples per tissue from each location to identify candidate genes which are involved in the adaptation of Korean commercial chicken to Kyrgyzstan. At false discovery rate (FDR) < 0.05 and fold change (FC) > 2, we found 315, 196, 167 and 198 genes in liver, breast, cecum, and gizzard respectively as differentially expressed between the two locations. GO enrichment analysis showed that these genes were highly enriched for cellular and metabolic processes, catalytic activity, and biological regulations. Similarly, KEGG pathways analysis indicated metabolic, PPAR signaling, FoxO, glycolysis/gluconeogenesis, biosynthesis, MAPK signaling, CAMs, citrate cycles pathways were differentially enriched. Enriched genes like TSKU,...
Heat stress (HS) negatively impacts pig production and swine health. Therefore, to understand the... more Heat stress (HS) negatively impacts pig production and swine health. Therefore, to understand the genetic and metabolic responses of pigs to HS, we used RNA-Seq and high resolution magic angle spinning (HR-MAS) NMR analyses to compare the transcriptomes and metabolomes of Duroc pigs (n = 6, 3 barrows and 3 gilts) exposed to heat stress (33 °C and 60% RH) with a control group (25 °C and 60% RH). HS resulted in the differential expression of 552 (236 up, 316 down) and 879 (540 up, 339 down) genes and significant enrichment of 30 and 31 plasma metabolites in female and male pigs, respectively. Apoptosis, response to heat, Toll-like receptor signaling and oxidative stress were enriched among the up-regulated genes, while negative regulation of the immune response, ATP synthesis and the ribosomal pathway were enriched among down-regulated genes. Twelve and ten metabolic pathways were found to be enriched (among them, four metabolic pathways, including arginine and proline metabolism, and...
ecotypes. This study provides information on the HS response of chickens, adapted to two differen... more ecotypes. This study provides information on the HS response of chickens, adapted to two different agro climatic environments, extending our understanding of the mechanisms of HS response and the effect of adaptation in counteracting HS.
International Journal for Computational Biology, 2015
A Drug designing is a process in which new leads (potential drugs) are discovered which have ther... more A Drug designing is a process in which new leads (potential drugs) are discovered which have therapeutic benefits in diseased condition. With development of various computational tools and availability of databases (having information about 3D structure of various molecules) discovery of drugs became comparatively, a faster process. The two major drug development methods are structure based drug designing and ligand based drug designing. Structure based methods try to make predictions based on three dimensional structure of the target molecules. The major approach of structure based drug designing is Molecular docking, a method based on several sampling algorithms and scoring functions. Docking can be performed in several ways depending upon whether ligand and receptors are rigid or flexible. Hotspot grafting, is another method of drug designing. It is preferred when the structure of a native binding protein and target protein complex is available and the hotspots on the interface are known. In absence of information of three Dimensional structure of target molecule, Ligand based methods are used. Two common methods used in ligand based drug designing are Pharmacophore modelling and QSAR. Pharmacophore modelling explains only essential features of an active ligand whereas QSAR model determines effect of certain property on activity of ligand. Fragment based drug designing is a de novo approach of building new lead compounds using fragments within the active site of the protein. All the candidate leads obtained by various drug designing method need to satisfy ADMET properties for its development as a drug. Insilico ADMET prediction tools have made ADMET profiling an easier and faster process. In this review, various softwares available for drug designing and ADMET property predictions have also been listed.
International Journal for Computational Biology, 2014
Repeat of amino acids in a protein sequence has clinical and functional importance. Database of P... more Repeat of amino acids in a protein sequence has clinical and functional importance. Database of Perfect Amino Acid Repeat (DPAAR) is a kind of relational as well as flat file database which is created by the comprehensive analysis of 5,42,782 protein sequences of Swiss-Prot database (released on 19 th March,2014) to know the association between repeated sequence and disease. It provides the search engine for rapid access of a particular repeated amino acid, or particular swissprot ID, or particular length of repeated amino acids in a protein sequence. It also provides the flat files for single, oligo, and tandem repeated sequence information to get the complete informaton about concerned amino acids repeat. It consists of the tables of repeated sequence and its associated disease in human being.
The microbial composition in the cecum of pig influences host health, immunity, nutrient digestio... more The microbial composition in the cecum of pig influences host health, immunity, nutrient digestion, and feeding requirements significantly. Advancements in metagenome sequencing technologies such as 16S rRNAs have made it possible to explore cecum microbial population. In this study, we performed a comparative analysis of cecum microbiota of crossbred Korean native pigs at two different growth stages (stage L = 10 weeks, and stage LD = 26 weeks) using 16S rRNA sequencing technology. Our results revealed remarkable differences in microbial composition, α and β diversity, and differential abundance between the two stages. Phylum composition analysis with respect to SILVA132 database showed Firmicutes to be present at 51.87% and 48.76% in stages L and LD, respectively. Similarly, Bacteroidetes were present at 37.28% and 45.98% in L and LD, respectively. The genera Prevotella, Anaerovibrio, Succinivibrio, Megasphaera were differentially enriched in stage L, whereas Clostridium, Terrispo...
Journal of Biomedical Translational Research, 2018
Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat... more Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP × Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (|log2FC| > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.
Positive results of many Trials have incorporated concurrent and sequential chemo radiotherapy in... more Positive results of many Trials have incorporated concurrent and sequential chemo radiotherapy in treatment of inoperable carcinoma esophagus. But concurrent chemo radiation therapy is similar to that achieved by surgery alone. The main plea of concurrent chemoradiation in esophageal cancers is early regression and palliation of dysphagia for long time. The aim of this study to analyse the modalities of treatment available for palliation of dysphagia in carcinoma esophagus and determine the most effective option among them. Materials and Methods: Between September 2011 to December 2013,50 patients of esophageal cancers were treated in our institute, 25 patients in sequential and 25 in concurrent chemo radiotherapy arm. Swallowing function was assessed in these patients by the use of a swallowing-function scoring system. Results: Assessment of response in two arms were done for grade of dysphagia palliation, Complete Response at 6 months and toxicity. Dysphagia scores improved in 88% in study arm and 64% in control arm. In study arm 28% male and 52% female patients, while in control arm 40 % male and 28% female patients presented with CR in primary tumor and mediastinal lymph node. There was statistical significant difference in toxicities of TLC and ANC between both arms. Grade 2 and 3 toxicities were 40% and 4% for TLC and were 28% and 0% for ANC in study and control arm respectively (p = 0.013 ,p=.014). This may be due to concurrent use of chemotherapy with radiation in study arm that also showed synergism for toxicity of TLC and ANC. Conclusion: Concurrent Chemo Radiotherapy is a more aggressive approach for dysphagia control, which is beneficial for those patients with good performance status .This approach is used as an alternative to stenting. This combination is more effective than neoadjuvant chemoradiation for improving dysphagia scores and QoL in inoperable esophageal cancers .
Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of... more Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of two oncogenes namely BCR and ABL with their aberrant expression. Autophosphorylation of BCR-ABL oncogenes results in proliferation of CML. The study deals with estimation of rate constant involved in each step of the cellular autophosphorylation process, which are consequently playing important roles in the proliferation of cancerous cells. Materials and Methods: A mathematical model was proposed for autophosphorylation of BCR-ABL oncogenes utilizing ordinary differential equations to enumerate the rate of change of each responsible system component. The major difficulty to model this process is the lack of experimental data, which are needed to estimate unknown model parameters. Initial concentration data of each substrate and product for BCR-ABL systems were collected from the reported literature. All parameters were optimized through time interval simulation using the fminsearch algorithm. Results: The rate of change versus time was estimated to indicate the role of each state variable that are crucial for the systems. The time wise change in concentration of substrate shows the convergence of each parameter in autophosphorylation process. Conclusions: The role of each constituent parameter and their relative time dependent variations in autophosphorylation process could be inferred.
Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on... more Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of-10.940 kcal/mol and Glide e-model score of-86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.
Interdisciplinary sciences, computational life sciences, Jan 16, 2016
Cereal grain bread wheat (T. aestivum) is an important source of food and belongs to Poaceae fami... more Cereal grain bread wheat (T. aestivum) is an important source of food and belongs to Poaceae family. Hypothetical proteins (HPs), i.e., proteins with unknown functions, share a substantial portion of wheat proteomes and play important roles in growth and physiology of plant system. Several functional annotations studies utilizing the protein sequences for characterization of role of individual protein in physiology of plant systems were being reported in recent past. In this study, an integrated pipeline of software/servers has been used for the identification and functional annotation of 124 unique HPs of T. aestivum considering available data in NCBI till date. All HPs were broadly annotated, out of which functions of 77 HPs were successfully assigned with high confidence level. Precisely functional annotation of remaining 47 HPs is also characterized with low confidence. Several latest versions of protein family databases, pathways information, genomics context methods and in sil...
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to ab... more Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc. In this study IL-6 pathways have been taken into consideration which induces JAK/STAT and MAPK pathways to decipher the CML progression stages. An attempt has been made to model these pathways with the help of ordinary differential equations (ODEs) and estimating unknown parameters through fminsearch optimization algorithm. Some of the specific component like STAT3, of the pathway has been analyzed in detail and their role in CML progression has been elucidated. The roles of STAT3 inhibitors into the treatment of CML have been thoroughly studied and optimum concentration of the inhibitors have been predicted.
Journal of biomolecular structure & dynamics, Jan 19, 2015
Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been p... more Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been proven as the prime cause of Chronic Myeloid Leukemia (CML). It has been established that tyrosine kinase domain of BCR-ABL protein is a potential therapeutic target for the treatment of CML. Imatinib is considered as a first generation drug that can inhibit the enzymatic action by inhibiting the ATP binding with BCR-ABL protein. Later on, insensitivity of CML cells towards Imatinib has been observed may be due to mutation in tyrosine kinase domain of the ABL receptor. Subsequently some other second generation drugs have also been reported viz. Baustinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib etc., which can able to combat against mutated domain of ABL tyrosine kinase protein. By taking into account of bioavailability and resistance developed, there is an utmost need to find some more inhibitors for the mutated ABL tyrosine kinase protein. For virtual screening, a dataset has been ge...
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Papers by himansu kumar