scholarly journals Differential BUM-HMM: a robust statistical modelling approach for detecting RNA flexibility changes in high-throughput structure probing data

2020 ◽  
Author(s):  
Paolo Marangio ◽  
Ka Ying Toby Law ◽  
Guido Sanguinetti ◽  
Sander Granneman
Keyword(s):  
Protein Binding ◽  
High Throughput ◽  
Conformational Changes ◽  
Binding Sites ◽  
Rna Structure ◽  
Structural Changes ◽  
High Throughput Sequencing ◽  
Structural Information ◽  
Protein Binding Sites ◽  
Structure Probing

Combining RNA structure probing with high-throughput sequencing technologies has greatly enhanced our ability to analyze RNA structure at transcriptome scale. However, the high level of noise and variability encountered in these data call for the development of computational tools that robustly extract RNA structural information. Here we present diffBUM-HMM, a noise-aware model that enables accurate detection of RNA flexibility and conformational changes from high-throughput RNA structure-probing data. DiffBUM-HMM is compatible with a wide variety of high-throughput RNA structure probing data, taking into consideration biological variation, sequence coverage and sequence representation biases. We demonstrate that, compared to the existing approaches, diffBUM-HMM displays higher sensitivity while calling virtually no false positives. DiffBUM-HMM analysis of ex vivo and in vivo Xist SHAPE-MaP data detected many more RNA structural differences, involving mostly single-stranded nucleotides located at or near protein-binding sites. Collectively, our analyses demonstrate the value of diffBUM-HMM for quantitatively detecting RNA structural changes and reinforce the notion that RNA structure probing is a very powerful tool for identifying protein-binding sites.

scholarly journals diffBUM-HMM: a robust statistical modeling approach for detecting RNA flexibility changes in high-throughput structure probing data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Paolo Marangio ◽  
Ka Ying Toby Law ◽  
Guido Sanguinetti ◽  
Sander Granneman
Keyword(s):  
High Throughput ◽  
Conformational Changes ◽  
Rna Structure ◽  
Structural Changes ◽  
Rna Binding ◽  
Structural Information ◽  
Sequence Coverage ◽  
Structure Probing ◽  
Generation Sequencing ◽  
Higher Sensitivity

AbstractAdvancing RNA structural probing techniques with next-generation sequencing has generated demands for complementary computational tools to robustly extract RNA structural information amidst sampling noise and variability. We present diffBUM-HMM, a noise-aware model that enables accurate detection of RNA flexibility and conformational changes from high-throughput RNA structure-probing data. diffBUM-HMM is widely compatible, accounting for sampling variation and sequence coverage biases, and displays higher sensitivity than existing methods while robust against false positives. Our analyses of datasets generated with a variety of RNA probing chemistries demonstrate the value of diffBUM-HMM for quantitatively detecting RNA structural changes and RNA-binding protein binding sites.

scholarly journals Computational identification of protein binding sites on RNAs using high-throughput RNA structure-probing data

2013 ◽  
Vol 30 (8) ◽  
pp. 1049-1055 ◽  
Author(s):  
Xihao Hu ◽  
Thomas K. F. Wong ◽  
Zhi John Lu ◽  
Ting Fung Chan ◽  
Terrence Chi Kong Lau ◽  
...  
Keyword(s):  
Protein Binding ◽  
High Throughput ◽  
Binding Sites ◽  
Rna Structure ◽  
Protein Binding Sites ◽  
Structure Probing ◽  
Computational Identification

scholarly journals FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing

2010 ◽  
Vol 7 (12) ◽  
pp. 995-1001 ◽  
Author(s):  
Jason G Underwood ◽  
Andrew V Uzilov ◽  
Sol Katzman ◽  
Courtney S Onodera ◽  
Jacob E Mainzer ◽  
...  
Keyword(s):  
High Throughput ◽  
Rna Structure ◽  
High Throughput Sequencing ◽  
Structure Probing

PROTEIN-RNA INTERACTIONS IN BACTERIAL RIBOSOMES

1973 ◽  
Vol 74 (Suppl) ◽  
pp. S75-S94 ◽  
Author(s):  
R. A. Garrett ◽  
H. G. Wittmann
Keyword(s):  
Protein Binding ◽  
Structural Properties ◽  
Conformational Changes ◽  
Binding Sites ◽  
Ribosomal Proteins ◽  
Structural Factors ◽  
Optimal Conditions ◽  
Protein Binding Sites ◽  
E Coli ◽  
Experimental Approaches

ABSTRACT There are several ribosomal proteins which can bind specifically to the three ribosomal RNA's of E. coli. Some structural properties of these proteins and of the RNA are described together with the optimal conditions for binding. Evidence for conformational changes occurring in some proteins, and in the RNA's during binding, is also discussed. The partial localisation of protein binding sites on the 16S and 5S RNA's, and for one protein on the 23S RNA has been attained recently. However, relatively little is known about the regions of the protein which interact with the RNA. Although the nature of the specificity of the protein-RNA interactions is not yet understood, some experimental approaches which are in progress to elucidate the basis of this specificity are mentioned together with a discussion of the structural factors which may be important.

EVALUATION OF TISSUE STEROID BINDING IN VITRO

1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S223-S246 ◽  
Author(s):  
C. R. Wira ◽  
H. Rochefort ◽  
E. E. Baulieu
Keyword(s):  
Protein Binding ◽  
Binding Sites ◽  
Experimental System ◽  
Specific Protein ◽  
Coupling Mechanism ◽  
Target Tissue ◽  
Protein Binding Sites ◽  
Definition Of ◽  
Hormone Specificity

ABSTRACT The definition of a RECEPTOR* in terms of a receptive site, an executive site and a coupling mechanism, is followed by a general consideration of four binding criteria, which include hormone specificity, tissue specificity, high affinity and saturation, essential for distinguishing between specific and nonspecific binding. Experimental approaches are proposed for choosing an experimental system (either organized or soluble) and detecting the presence of protein binding sites. Techniques are then presented for evaluating the specific protein binding sites (receptors) in terms of the four criteria. This is followed by a brief consideration of how receptors may be located in cells and characterized when extracted. Finally various examples of oestrogen, androgen, progestagen, glucocorticoid and mineralocorticoid binding to their respective target tissues are presented, to illustrate how researchers have identified specific corticoid and mineralocorticoid binding in their respective target tissue receptors.

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