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A "fuzzy"-logic language for encoding multiple physical traits in biomolecules.

ABSTRACT: To carry out their activities, biological macromolecules balance different physical traits, such as stability, interaction affinity, and selectivity. How such often opposing traits are encoded in a macromolecular system is critical to our understanding of evolutionary processes and ability to design new molecules with desired functions. We present a framework for constraining design simulations to balance different physical characteristics. Each trait is represented by the equilibrium fractional occupancy of the desired state relative to its alternatives, ranging from none to full occupancy, and the different traits are combined using Boolean operators to effect a "fuzzy"-logic language for encoding any combination of traits. In another paper, we presented a new combinatorial backbone design algorithm AbDesign where the fuzzy-logic framework was used to optimize protein backbones and sequences for both stability and binding affinity in antibody-design simulation. We now extend this framework and find that fuzzy-logic design simulations reproduce sequence and structure design principles seen in nature to underlie exquisite specificity on the one hand and multispecificity on the other hand. The fuzzy-logic language is broadly applicable and could help define the space of tolerated and beneficial mutations in natural biomolecular systems and design artificial molecules that encode complex characteristics.

SUBMITTER: Warszawski S

PROVIDER: S-EPMC4270444 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM) performed poorly in inferring transcriptional interactions (TIs), which represent physical interactions between transcription factors (TF) and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM) was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning) fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy.ResultsAdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF), and using 19 transcription factors (TFs), we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms.ConclusionAdaFuzzy successfully integrates multiple types of data (sequence, ChIP, and microarray) to predict transcriptional regulatory networks. The validated success in the prediction results implies that AdaFuzzy can be applied to uncover TIs in yeast.

Project description:Similarity measure, also called information measure, is a concept used to distinguish different objects. It has been studied from different contexts by employing mathematical, psychological, and fuzzy approaches. Image steganography is the art of hiding secret data into an image in such a way that it cannot be detected by an intruder. In image steganography, hiding secret data in the plain or non-edge regions of the image is significant due to the high similarity and redundancy of the pixels in their neighborhood. However, the similarity measure of the neighboring pixels, i.e., their proximity in color space, is perceptual rather than mathematical. Thus, this paper proposes an interval type-2 fuzzy logic system (IT2 FLS) to determine the similarity between the neighboring pixels by involving an instinctive human perception through a rule-based approach. The pixels of the image having high similarity values, calculated using the proposed IT2 FLS similarity measure, are selected for embedding via the least significant bit (LSB) method. We term the proposed procedure of steganography as 'IT2 FLS-LSB method'. Moreover, we have developed two more methods, namely, type-1 fuzzy logic system based least significant bits (T1FLS-LSB) and Euclidean distance based similarity measures for least significant bit (SM-LSB) steganographic methods. Experimental simulations were conducted for a collection of images and quality index metrics, such as PSNR (peak signal-to-noise ratio), UQI (universal quality index), and SSIM (structural similarity measure) are used. All the three steganographic methods are applied on dataset and the quality metrics are calculated. The obtained stego images and results are shown and thoroughly compared to determine the efficacy of the IT2 FLS-LSB method. We have also demonstrated the high payload capacity of our proposed method. Finally, we have done a comparative analysis of the proposed approach with the existing well-known steganographic methods to show the effectiveness of our proposed steganographic method.

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A "fuzzy"-logic language for encoding multiple physical traits in biomolecules.

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