scholarly journals MBCL-20. DETECTION OF SOMATIC MUTATIONS BY USING RNA-SEQ DATA IN CHILDHOOD MEDULLOBLASTOMA AND ITS POTENTIAL CLINICAL APPLICATION: A COHORT SERIES OF 52 CASES STUDY IN TAIWAN

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii392-iii392
Author(s):  
Tai-Tong Wong ◽  
Kuo-Sheng Wu ◽  
Donald Ming-Tak Ho ◽  
Shih-Chieh Lin ◽  
Wen-Chang Huang ◽  
...  
Keyword(s):  
Clinical Application ◽  
Genetic Predisposition ◽  
Drug Targets ◽  
Clinical Findings ◽  
Driver Mutations ◽  
Potential Drug ◽  
Rna Seq ◽  
Methylation Array ◽  
Childhood Medulloblastoma ◽  
Potential Drug Targets

Abstract BACKGROUND In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). Part of our aim was to explore the clinical application for drug target identification and finding clues to genetic predisposition. METHODS In total, 52 frozen tumor tissues of childhood MBs were collected. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping was performed. We selected 51 clinically relevant genes for somatic variant calling using RNA-Seq data. Correlated clinical findings to genetic predisposition were defined. Potential drug targets and genetic predispositions were explored. RESULTS Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Potential drug targets were detected in the pathways of DNA damage response. Five patients with relevant clinical findings to genetic predisposition clustered in SHH MBs. The corresponding somatic driver mutations involved TP53, MSH6, PTEN, PTCH1, and TERT promoter (suspicious). For validation, whole exome sequencing (WES) of blood and tumor tissue was used in 10 patients with SHH MBs in the cohort series. This study included the five patients with potential genetic predispositions. Four patients exhibited relevant germline mutations named as TP53, MSH6, PTEN, and SUFU. CONCLUSION The findings of this study provide valuable information for personalized care of childhood MB in our cohort series and in Taiwan.

scholarly journals Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 653
Author(s):  
Kuo-Sheng Wu ◽  
Donald Ming-Tak Ho ◽  
Shiann-Tarng Jou ◽  
Alice L. Yu ◽  
Huy Minh Tran ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Drug Targets ◽  
Tumor Resection ◽  
Potential Drug ◽  
Clinical Correlation ◽  
Rna Seq ◽  
Methylation Array ◽  
Personalized Care ◽  
Pediatric Medulloblastoma ◽  
Potential Drug Targets

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan.

Proteomic and Bioinformatic Analysis of Trypanosoma cruzi Chemotherapy and Potential Drug Targets: New Pieces for an Old Puzzle

2014 ◽  
Vol 15 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Rubem Sadok Menna-Barreto ◽  
Kele Belloze ◽  
Jonas Perales ◽  
Floriano Silva-Jr
Keyword(s):  
Trypanosoma Cruzi ◽  
Drug Targets ◽  
Bioinformatic Analysis ◽  
Potential Drug ◽  
Potential Drug Targets

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals Plasmodium Kinases as Potential Drug Targets for Malaria: Challenges and Opportunities

2021 ◽  
Vol 7 (3) ◽  
pp. 518-534
Author(s):  
Lauren B. Arendse ◽  
Susan Wyllie ◽  
Kelly Chibale ◽  
Ian H. Gilbert
Keyword(s):  
Drug Targets ◽  
Potential Drug ◽  
Challenges And Opportunities ◽  
Potential Drug Targets

scholarly journals In silico characterization and structural modeling of bacterial metalloprotease of family M4

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rajnee Hasan ◽  
Md. Nazmul Haq Rony ◽  
Rasel Ahmed
Keyword(s):  
Drug Targets ◽  
Active Sites ◽  
Pathogenic Bacteria ◽  
Tertiary Structure ◽  
Transmembrane Helix ◽  
Confidence Score ◽  
Potential Drug ◽  
Protein Protein Interaction ◽  
Industrial Level ◽  
Potential Drug Targets

Abstract Background The M4 family of metalloproteases is comprised of a large number of zinc-containing metalloproteases. A large number of these enzymes are important virulence factors of pathogenic bacteria and therefore potential drug targets. Whereas some enzymes have potential for biotechnological applications, the M4 family of metalloproteases is known almost exclusively from bacteria. The aim of the study was to identify the structure and properties of M4 metalloprotease proteins. Results A total of 31 protein sequences of M4 metalloprotease retrieved from UniProt representing different species of bacteria have been characterized for various physiochemical properties. They were thermostable, hydrophillic protein of a molecular mass ranging from 38 to 66 KDa. Correlation on the basis of both enzymes and respective genes has also been studied by phylogenetic tree. B. cereus M4 metalloprotease (PDB ID: 1NPC) was selected as a representative species for secondary and tertiary structures among the M4 metalloprotease proteins. The secondary structure displaying 11 helices (H1-H11) is involved in 15 helix-helix interactions, while 4 β-sheet motifs composed of 15 β-strands in PDBsum. Possible disulfide bridges were absent in most of the cases. The tertiary structure of B. cereus M4 metalloprotease was validated by QMEAN4 and SAVES server (Ramachandran plot, verify 3D, and ERRAT) which proved the stability, reliability, and consistency of the tertiary structure of the protein. Functional analysis was done in terms of membrane protein topology, disease-causing region prediction, proteolytic cleavage sites prediction, and network generation. Transmembrane helix prediction showed absence of transmembrane helix in protein. Protein-protein interaction networks demonstrated that bacillolysin of B. cereus interacted with ten other proteins in a high confidence score. Five disorder regions were identified. Active sites analysis showed the zinc-binding residues—His-143, His-147, and Glu-167, with Glu-144 acting as the catalytic residues. Conclusion Moreover, this theoretical overview will help researchers to get a details idea about the protein structure and it may also help to design enzymes with desirable characteristics for exploiting them at industrial level or potential drug targets.

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