Elebeoba E. May

Coding model for translation in E. coli K-12

Various computational methods for determining protein producing regions in a given genome are based on engineering constructs such as hidden Markov models and neural networks. The work presents a coding theory approach to modeling the process of protein translation initiation. The messenger RNA (mRNA) is viewed as a noisy encoded message and the ribosome as a block code minimum distance decoder. The results of applying this model to the Escherichia coli K-12 are presented.

The ribosome as a table-driven convolutional decoder for the Escherichia coli K-12 translation initiation system

Redundancy occurs naturally within RNA and DNA sequences. The existence of tandem repeats, and sequences such as the Shine-Dalgarno sequence, the Pribnow box and the TATA box, leads the authors to believe that cellular communication systems use some method of coding to recognize valid information regions within a nucleotide sequence and correct for transmission errors such as mutations. Here, the authors use principles of convolutional coding theory to analyse the translation initiation process. The principle hypothesis is that the messenger RNA (mRNA) sequence can be viewed as a noisy, convolutionary encoded signal. The ribosome is functionally paralleled to a table-driven convolutional decoder. The 16s ribosomal RNA (rRNA) sequence is used to form decoding masks for table-driven decoding. The results of applying this method to Escherichia coli K-12 strain MG1655 are presented.

Free energy periodicity in E. coli coding

Sequences upstream from coding regions in E. coli commonly possess significant complementarity to the exposed part of the 16S rRNA. This region is known as the Shine-Dalgarno sequence. Free energy calculations for binding between homologous sequences suggest that this region is used as a landing site for construction of the ribosome around the mRNA. While strong upstream binding appears to be a condition for translation, it may not be sufficient. The authors research suggests that the 16S has a continuing role throughout translation, particularly in ribosomal synchronization with the reading frame. The authors consider the entire E. coli genome of over 2000 forward coding sequences. Presence of strong upstream binding is confirmed, and a definite three-base periodic signal is observed. The distribution of bases parallels that needed to produce a signal of the type observed.

Constructing optimal convolutional code models for prokaryotic translation initiation

Rapid advances in both genomic data acquisition and computational technology have encouraged the development and use of engineering methods in the field of bioinformatics and computational genomics. Several researchers are encouraging the use of error-correction coding in analyzing genetic data. Using information theory, coding theory specifically, the translation of messenger RNA (mRNA) into amino acid sequences is functionally paralleled to the decoding of noisy, convolutionally encoded parity streams. The ribosome is modeled as a table-based convolutional decoder. This work presents a genetic algorithms (GAs) method for the design of optimal table-based convolutional coding models for prokaryotic translation initiation sites using Escherichia coli K-12 as the model organism. We explore and compare several categories of error-control codes, including: horizontal, vertical, equal and unequal error protection (UEP) codes. Results show that UEP code models recognize the non-random and Shine-Dalgarno domain of mRNA leaders better than equal error protection models. Codes whose decoding masks (gmasks) have high similarity to the 3 end of the 16S ribosomal RNA (rRNA) were discovered. Additional results are presented.

Free energy periodicity in E.coli

It has been seen that sequences upstream from coding regions tend to possess significant complementarity to the exposed part of the 16S rRNA in E.coli. While upstream binding between the Shine-Dalgarno sequence and the mRNA may be a necessary condition for translation, it appears to be insufficient. By computing the free energy binding within the coding sequence, it is suggested that the 16S has a continuing role through elongation of translation as well.

Communication theory and molecular biology at the crossroads

This paper endeavors to explore ideas at the crossroads of communication theory and molecular biology from various disciplinary backgrounds and vantage points, providing an overview of the state of research and making compelling observations regarding the nature of biological information transmission in light of the principles of digital communication. The paper also focuses on whether evidence of coding theoretic properties exists in biology and if such evidence supports information or coding theory view of genetics. The successful development of biological information and coding can provide a theoretical basis for understanding, quantifying, and engineering error control in natural and synthesized biosystems. The intersection of communication theory and molecular biology could potentially yield a quantitative framework for engineering fault-tolerant genes, proteins, and genomes that approach an organisms communication capacity. Immediate applications of coding theory and coding theoretic principles to genomics are presented.

The dynamic immunomodulatory effects of vitamin D3 during Mycobacterium infection

Mycobacterium tuberculosis (Mtb), is a highly infectious airborne bacterium. Previous studies have found vitamin D3 to be a key factor in the defense against Mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. Mycobacterium smegmatis was used in our study as a surrogate of Mtb. We hypothesized that the continuous presence of vitamin D3, as well as the level of severity of infection would differentially modulate host cell immune response in comparison with control and the vehicle, ethanol. We found that vitamin D3 conditioning promotes increased bacterial clearance during low-level infection, intracellular containment during high-level infection, and minimizes host cytotoxicity. In the presence of vitamin D3 host cell production of cytokines and effector molecules was infection-level dependent, most notably IL-12, which increased during high-level infection and decreased during low-level infection, and NO, which had a rate of change positively correlated to IL-12. Our study provides evidence that vitamin D3 modulation is context-dependent and time-variant, as well as highly correlated to level of infection. This study furthers our mechanistic understanding of the dual role of vitamin D3 as a regulator of bactericidal molecules and protective agent against host cell damage.

Syndrome-Based Discrimination of Single Nucleotide Polymorphism

The ability to discriminate nucleic acid sequences is necessary for a wide variety of applications: high throughput screening, distinguishing genetically modified organisms (GMOs), molecular computing, differentiating biological markers, fingerprinting a specific sensor response for complex systems, etc. Hybridization-based target recognition and discrimination is central to the operation of nucleic acid sensor systems. Therefore developing a quantitative correlation between mishybridization events and sensor out put is critical to the accurate interpretation of results. In this work, using experimental data produced by introducing single mutations (single nucleotide polymorphisms, SNPs) in the probe sequence of computational catalytic molecular beacons (deoxyribozyme gates) [1], we investigate coding theory algorithms for uniquely categorizing SNPs based on the calculation of syndromes

Binding motif based code models for prokaryotic translation initiation

Studies of prokaryotic translation initiation sites reveal that ribosomal binding sites appear to evolve to functional requirements rather than to genetic sequences that produce the strongest binding site. Several factors influence translation of mRNA sequences, including: initiation codon, presence and location of the Shine-Dalgarno sequence, spacing between the initiation codon and the Shine-Dalgarno domain, the second codon following the initiator codon, and possibly other nucleotides in the -20 to +13 region of the mRNA leader region. These factors influence how the small subunit of the ribosome interacts with and binds to the mRNA leader region such that conditions are favorable for successful translation initiation. In this work translation initiation models are constructed by analyzing possible binding patterns between mRNA leader sequences and the exposed portion of the 16S rRNA. Binding analysis data are used as inputs to a genetic algorithm which searches for optimal binary, convolutional codes to model the Eschericha coli K-12 translation initiation system. We present an evaluation of the coding models discovered.