Bioinformatic analysis
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To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots. Struct. Funct. Genet., 41:271-287)] and dinucleotide conformers [Svozil, Kalina, Omelka and Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids Res., 36:3690-3706)], respectively. Assembling the mutually interacting protein blocks and dinucleotide conformers into 'interaction matrices' revealed their correlations and conformer preferences at the interface relative to their occurrence outside the interface. The analyzed data demonstrated important differences between complexes of various types of proteins such as transcription factors and nucleases, distinct interaction patterns for the DNA minor groove relative to the major groove and phosphate and importance of water-mediated contacts. Water molecules mediate proportionally the largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors. The generally known induction of A-DNA forms by complexation was more accurately attributed to A-like and intermediate A/B conformers rare in naked DNA molecules.
- MeSH
- DNA vazebné proteiny chemie MeSH
- DNA chemie MeSH
- fosfáty MeSH
- interpretace statistických dat MeSH
- konformace nukleové kyseliny MeSH
- konformace proteinů MeSH
- molekulární modely MeSH
- vazba proteinů MeSH
- voda chemie MeSH
- výpočetní biologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Metoda sekvenování nové generace (NGS) se stala velmi populární v biomedicínském výzkumu i v klinické praxi zejména proto, že umožňuje rychlý a detailní vhled do genomu pacienta. V kontextu nádorových onemocnění umožňují metody NGS přesnou detekci jak zárodečných záměn, tak zejména somatických mutací, které mohou pomoci rychle a precizně stanovit diagnózu a přizpůsobit léčbu podle individuálních potřeb pacienta. Vývojem nových výpočetních metod a jejich aplikací za účelem precizního zpracování NGS dat se zabývá vědní obor bioinformatika. Bioinformatická analýza je komplexní proces, jehož správné nastavení je klíčové pro získání relevantních výsledků. Je proto nutné, aby bioinformatik detailně porozuměl biologické podstatě sledovaného jevu, jako je například vznik genových mutací v průběhu onemocnění. Z hlediska bioanalytika i lékaře je naopak užitečné znát jak možnosti a limity NGS technologie, tak i základní bioinformatickou terminologii, na základě které jsou pak schopni s bioinformatiky efektivně komunikovat. V této souhrnné práci se proto autoři snaží obecně popsat bioinformatickou analýzu sekvenačních dat s důrazem na vysvětlení základních pojmů používaných v oblasti analýzy NGS dat.
Next generation sequencing (NGS) has become very popular both in research and clinical practice, in particular because it allows detailed and rapid insight into the patients genome, which can help to diagnose a disease quickly and precisely and thus enable treatment administration based on individual patient needs. The development of novel computing methods and their application for accurate processing of NGS data is the objective of the scientific field of bioinformatics. Bioinformatic analysis is a complex process and its precise set-up is absolutely crucial for obtaining relevant results. Thus, it is necessary for bioinformaticians to understand the biological principles of the given analysis, such as the development of somatic mutations during disease course. From the perspective of a bio-analyst or physician, it is essential to understand the challenges and limits of NGS technology; basic knowledge of bioinformatics and its terminology allows for effective communication with bioinformaticians. In this review, the authors attempt to describe bioinformatic analysis with emphasis on explaining the basic concepts used in the NGS data analysis.
- Klíčová slova
- sekvenování nové generace (NGS),
- MeSH
- lidé MeSH
- sekvenční analýza DNA * metody trendy MeSH
- výpočetní biologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Molecular profiling of tumor samples has acquired importance in cancer research, but currently also plays an important role in the clinical management of cancer patients. Rapid identification of genomic aberrations improves diagnosis, prognosis and effective therapy selection. This can be attributed mainly to the development of next-generation sequencing (NGS) methods, especially targeted DNA panels. Such panels enable a relatively inexpensive and rapid analysis of various aberrations with clinical impact specific to particular diagnoses. In this review, we discuss the experimental approaches and bioinformatic strategies available for the development of an NGS panel for a reliable analysis of selected biomarkers. Compliance with defined analytical steps is crucial to ensure accurate and reproducible results. In addition, a careful validation procedure has to be performed before the application of NGS targeted assays in routine clinical practice. With more focus on bioinformatics, we emphasize the need for thorough pipeline validation and management in relation to the particular experimental setting as an integral part of the NGS method establishment. A robust and reproducible bioinformatic analysis running on powerful machines is essential for proper detection of genomic variants in clinical settings since distinguishing between experimental noise and real biological variants is fundamental. This review summarizes state-of-the-art bioinformatic solutions for careful detection of the SNV/Indels and CNVs for targeted sequencing resulting in translation of sequencing data into clinically relevant information. Finally, we share our experience with the development of a custom targeted NGS panel for an integrated analysis of biomarkers in lymphoproliferative disorders.
- Publikační typ
- časopisecké články MeSH
... , 171 -- 8 Predictive Methods Using Protein Sequences, 197 -- 9 Protein Structure Prediction and Analysis ... ... Wolfsberg -- PART TWO -- ANALYSIS AT THE NUCLEOTIDE LEVEL -- 5 Predictive Methods Using DNA Sequences ... ... Mullikin and Stephen T Sherry -- PART THREE -- ANALYSIS AT THE PROTEIN LEVEL -- 8 Predictive Methods ... ... Baxevanis -- I 2 Creation and Analysis of Protein Multiple Sequence Alignments, 325 -- Geoffrey J. ... ... Bouffard -- I 4 Phylogenetic Analysis, 365 -- Fiona S. ...
3rd ed. xviii, 540 s. : il. ; 29 cm
The expression of the main cytochrome P450 enzyme CYP3A4 displays enormous interindividual variability. Studies addressing the genetic variability of either the CYP3A4 gene itself or its key transcription factors have not found any crucial polymorphism contributing to this variability in expression, a phenomenon is referred to as the “missing heritability of CYP3A4 variability.” Several reports have recently described microRNAs (miRNAs) targeting the CYP3A4 gene and/or its major transcription factors. A comprehensive bioinformatic analysis was performed using the miRDB, PITA, miRanda and TargetScan programs in the search for hypothetical miRNAs targeting 3′-untranslated regions of PXR, CAR, VDR, HNF4α, RXRα, SHP and GRα genes controlling CYP3A4 expression. We propose several novel miRNAs identified parallelly by at least three algorithms to the target analyzed genes. In particular, we found novel promising miRNAs which may be involved in the indirect PXR-mediated CYP3A4 gene expression such as miR-18a and miR-18b, miR-449a, miR-449b and miR-34a. We also hypothesize that some miRNAs may play the role of a master regulator of NRs since they are predicted to target more than three genes. The identification of miRNAs determining CYP3A4 interindividual variability might be an important step toward progress in pharmacogenetics and personalized medicine.
- Klíčová slova
- jaderné receptory regulující expresi genu CYP3A4,
- MeSH
- biotransformace genetika imunologie účinky léků MeSH
- cytochrom P-450 CYP3A farmakologie genetika účinky léků MeSH
- farmakogenetika metody trendy MeSH
- genetický výzkum MeSH
- individualizovaná medicína metody trendy MeSH
- lidé MeSH
- mikro RNA * farmakologie genetika imunologie MeSH
- regulace genové exprese * genetika imunologie MeSH
- systém (enzymů) cytochromů P-450 genetika účinky léků MeSH
- výpočetní biologie metody trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The Practical approach series
xxvii, 418 s. : il. ; 25 cm
- MeSH
- výpočetní biologie MeSH
- Konspekt
- Biologické vědy
- NLK Obory
- biologie
- NLK Publikační typ
- kolektivní monografie
Methods of biochemical analysis ; v. 39
370 s. : il.
- Klíčová slova
- Laboratorní technika,
- MeSH
- databáze genetické MeSH
- klinické laboratorní techniky MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza MeSH
- výpočetní biologie MeSH
- Konspekt
- Biotechnologie. Genetické inženýrství
- NLK Obory
- lékařská informatika
- biomedicínské inženýrství
Ameloblastin (AMBN) was originally believed to be an enamel-specific extracellular matrix glycoprotein secreted by ameloblasts. Recently, AMBN expression was also detected in developing mesenchymal dental hard tissues, in trauma-induced reparative dentin, and during early craniofacial bone formation. The function and structure of AMBN still remain ambiguous, and there are no known proteins with similar primary sequences. We therefore performed a bio-informatic analysis of AMBN to model ab initio the three-dimensional structure of the molecule. The results suggest that AMBN is a two-domain, intrinsically unstructured protein (IUP). The analysis did not reveal any regions with structural similarity to known receptor-ligand systems, and did not identify any higher-order structures similar to functional regions in other known sequences. The AMBN model predicts 11 defined regions exposed on the surface, internalizing the rest of the molecule including a human-specific insert. Molecular dynamics analysis identified one specific and several non-specific calcium-binding regions, mostly at the C-terminal part of the molecule. The model is supported by previous observations that AMBN is a bipolar calcium-binding molecule and hints at a possible role in protein-protein interactions. The model provides information useful for further studies on the function of AMBN.
... -- Alignment of Pairs of Sequences, 65 Chapter 4 -- Introduction to Probability and Statistical Analysis ... ... Regulation, 361 Chapter 10 -- Protein Classification and Structure Prediction, 409 -- Chapter 11 Genome Analysis ... ... , 495 -- Chapter 1 2 -- Bioinformatics Programming Using Perl and Perl Modules, 549 -- Chapter 1 3 -- ... ... Analysis of Microarrays, 611 -- Index, 667 vii ...
2nd ed. xii, 692 s. : il.
- MeSH
- biologické vědy MeSH
- genetika MeSH
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
