scholarly journals Biological screens from linear codes: theory and tools

2015 ◽  
Author(s):  
Yaniv Erlich ◽  
Anna Gilbert ◽  
Hung Ngo ◽  
Atri Rudra ◽  
Nicolas Thierry-Mieg ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Molecular Biology ◽  
Small Molecules ◽  
Linear Codes ◽  
General Purpose ◽  
Light Weight ◽  
Pooling Designs ◽  
Systematic Testing ◽  
Mathematical Properties ◽  
Combinatorial Pooling

Molecular biology increasingly relies on large screens where enormous numbers of specimens are systematically assayed in the search for a particular, rare outcome. These screens include the systematic testing of small molecules for potential drugs and testing the association between genetic variation and a phenotype of interest. While these screens are ``hypothesis-free,'' they can be wasteful; pooling the specimens and then testing the pools is more efficient. We articulate in precise mathematical ways the type of structures useful in combinatorial pooling designs so as to eliminate waste, to provide light weight, flexible, and modular designs. We show that Reed-Solomon codes, and more generally linear codes, satisfy all of these mathematical properties. We further demonstrate the power of this technique with Reed-Solomon-based biological experiments. We provide general purpose tools for experimentalists to construct and carry out practical pooling designs with rigorous guarantees for large screens.

scholarly journals Improving Precise CRISPR Genome Editing by Small Molecules: Is there a Magic Potion?

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1318 ◽  
Author(s):  
Nadja Bischoff ◽  
Sandra Wimberger ◽  
Marcello Maresca ◽  
Cord Brakebusch
Keyword(s):  
Gene Therapy ◽  
Dna Repair ◽  
Animal Models ◽  
Molecular Biology ◽  
Small Molecules ◽  
Genome Editing ◽  
Drug Targets ◽  
Targeted Mutagenesis ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome editing has become a standard method in molecular biology, for the establishment of genetically modified cellular and animal models, for the identification and validation of drug targets in animals, and is heavily tested for use in gene therapy of humans. While the efficiency of CRISPR mediated gene targeting is much higher than of classical targeted mutagenesis, the efficiency of CRISPR genome editing to introduce defined changes into the genome is still low. Overcoming this problem will have a great impact on the use of CRISPR genome editing in academic and industrial research and the clinic. This review will present efforts to achieve this goal by small molecules, which modify the DNA repair mechanisms to facilitate the precise alteration of the genome.

scholarly journals High differentiation in functional traits but similar phenotypic plasticity in populations of a soil specialist along a climatic gradient

2020 ◽  
Vol 125 (6) ◽  
pp. 969-980 ◽  
Author(s):  
Silvia Matesanz ◽  
Marina Ramos-Muñoz ◽  
Mario Blanco-Sánchez ◽  
Adrián Escudero
Keyword(s):  
Genetic Variation ◽  
Phenotypic Plasticity ◽  
Functional Traits ◽  
Common Garden ◽  
Population Level ◽  
General Purpose ◽  
Climatic Conditions ◽  
Environment Interaction ◽  
Moisture Variation ◽  
Neutral Genetic Variation

Abstract Background and Aims Plants experiencing contrasting environmental conditions may accommodate such heterogeneity by expressing phenotypic plasticity, evolving local adaptation or a combination of both. We investigated patterns of genetic differentiation and plasticity in response to drought in populations of the gypsum specialist Lepidium subulatum. Methods We created an outdoor common garden with rain exclusion structures using 60 maternal progenies from four distinct populations that substantially differ in climatic conditions. We characterized fitness, life history and functional plasticity in response to two contrasting treatments that realistically reflect soil moisture variation in gypsum habitats. We also assessed neutral genetic variation and population structure using microsatellite markers. Key Results In response to water stress, plants from all populations flowered earlier, increased allocation to root tissues and advanced leaf senescence, consistent with a drought escape strategy. Remarkably, these probably adaptive responses were common to all populations, as shown by the lack of population × environment interaction for almost all functional traits. This generally common pattern of response was consistent with substantial neutral genetic variation and large differences in population trait means. However, such population-level trait variation was not related to climatic conditions at the sites of origin. Conclusions Our results show that, rather than ecotypes specialized to local climatic conditions, these populations are composed of highly plastic, general-purpose genotypes in relation to climatic heterogeneity. The strikingly similar patterns of plasticity among populations, despite substantial site of origin differences in climate, suggest past selection on a common norm of reaction due to similarly high levels of variation within sites. It is thus likely that plasticity will have a prevalent role in the response of this soil specialist to further environmental change.

scholarly journals Genetic variability of hepatitis A virus

2003 ◽  
Vol 84 (12) ◽  
pp. 3191-3201 ◽  
Author(s):  
Mauro Costa-Mattioli ◽  
Anna Di Napoli ◽  
Virginie Ferré ◽  
Sylviane Billaudel ◽  
Raul Perez-Bercoff ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Molecular Biology ◽  
Genetic Variability ◽  
Molecular Epidemiology ◽  
Mutation Rate ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Genetic Recombination ◽  
Classification Methods ◽  
Evolutionary Mechanisms

Knowledge of the molecular biology of hepatitis A virus (HAV) has increased exponentially since its identification. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. HAV has been characterized by the emergence of different genotypes, three human antigenic variants and only one major serotype. This paper reviews the genetic variability and molecular epidemiology of HAV. Its evolutionary mechanisms are described with particular emphasis on genetic recombination and HAV mutation rate. Genotypic classification methods are also discussed.

scholarly journals Targeting RNA structures in diseases with small molecules

2020 ◽  
Vol 64 (6) ◽  
pp. 955-966 ◽  
Author(s):  
Yanqiu Shao ◽  
Qiangfeng Cliff Zhang
Keyword(s):  
Gene Expression ◽  
Molecular Biology ◽  
Small Molecules ◽  
Structural Biology ◽  
Rna Structure ◽  
Therapeutic Potential ◽  
Rna Structures ◽  
Gene Expression And Regulation ◽  
Cellular Processes ◽  
Target Rna

Abstract RNA is crucial for gene expression and regulation. Recent advances in understanding of RNA biochemistry, structure and molecular biology have revealed the importance of RNA structure in cellular processes and diseases. Various approaches to discovering drug-like small molecules that target RNA structure have been developed. This review provides a brief introduction to RNA structural biology and how RNA structures function as disease regulators. We summarize approaches to targeting RNA with small molecules and highlight their advantages, shortcomings and therapeutic potential.

7. Molecular biology in the clinic

2016 ◽  
Author(s):  
Aysha Divan ◽  
Janice A. Royds
Keyword(s):  
Genetic Variation ◽  
Molecular Biology ◽  
Clinical Research ◽  
Clinical Efficacy ◽  
Molecular Basis ◽  
Disease Risk ◽  
Molecular Pathways ◽  
Epigenetic Changes ◽  
Cellular Processes ◽  
Environmental Agents

Environmental agents can cause genetic and epigenetic changes to DNA, the consequences of which lead to deregulation of cellular processes and pathways that cause disease. Genetic variation can either be inherited if acquired through the germline or non-heritable when the DNA changes occur in somatic (body) cells. ‘Molecular biology in the clinic’ discusses two key contemporary areas of clinical research that have benefited from an improved knowledge of their molecular basis: ageing and cancer. It shows that we are now better able to predict disease risk and design drugs that have higher clinical efficacy by targeting specific molecular pathways.

scholarly journals Graphics card processing: accelerating profile-profile alignment

2012 ◽  
Vol 2 (4) ◽  
Author(s):  
Muhammad Hanif ◽  
Karl-Heinz Zimmermann
Keyword(s):  
Molecular Biology ◽  
General Purpose ◽  
Matrix Product ◽  
Fundamental Operation ◽  
Computational Power ◽  
Multiple Sequence ◽  
Average Speed ◽  
Order Of Magnitude ◽  
Speed Up ◽  
Profile Alignment

AbstractAlignment is the fundamental operation in molecular biology for comparing biomolecular sequences. The most widely used method for aligning groups of alignments is based on the alignment of the profiles corresponding to the groups. We show that profile-profile alignment can be significantly speeded up by general purpose computing on a modern commodity graphics card. Wavefront and matrix-matrix product approaches for implementing profile-profile alignment onto graphics processor are analyzed. The average speed-up obtained is one order of magnitude even when overheads are considered. Thus the computational power of graphics cards can be exploited to develop improved solutions for multiple sequence alignment.

scholarly journals Kangaroo gene mapping and sequencing: insights into mammalian genome evolution

2013 ◽  
Vol 61 (1) ◽  
pp. 4 ◽  
Author(s):  
Jennifer A. Marshall Graves
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Molecular Biology ◽  
Dna Sequence ◽  
Sex Chromosomes ◽  
Chromosome Pair ◽  
Regulation Of Gene Expression ◽  
Mammalian Genome ◽  
Epigenetic Silencing ◽  
Gene Arrangement

The deep divergence of marsupials and eutherian mammals 160 million years ago provides genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. Following the pioneering work of Professor Desmond W. Cooper, emerging techniques in cytogenetics and molecular biology have been adapted to characterise the genomes of kangaroos and other marsupials. In particular, genetic and genomic work over four decades has shown that marsupial sex chromosomes differ significantly from the eutherian XY chromosome pair in their size, gene content and activity. These differences can be exploited to deduce how mammalian sex chromosomes, sex determination and epigenetic silencing evolved.

Chemical studies of the combining sites of antibodies

1966 ◽  
Vol 166 (1003) ◽  
pp. 188-206 ◽  
Keyword(s):  
Immune Response ◽  
Molecular Biology ◽  
Small Molecules ◽  
Chemical Structure ◽  
Biological Function ◽  
Naturally Occurring ◽  
Synthetic Polypeptides ◽  
Chemical Studies ◽  
Antibody Structure ◽  
Synthetic Antigens

Recent advances in molecular biology have permitted significant progress in correlating the chemical structure and biological function of naturally occurring macromolecules. The problem of the nature and mechanism of the immune response is a field of molecular biology which still poses many difficulties at both the cellular and the molecular level. The heterogeneity of antibodies is an outstanding example of these difficulties. One of the approaches to a better understanding of the chemical basis of immunological phenomena was the use of simple and well-defined molecules as elicitors of the various types of immune response. The use of synthetic polypeptides, polypeptidyl proteins, and of conjugates of various small molecules with synthetic polypeptides in studies of the molecular basis of immunological phenomena (for review, see Sela 1966) facilitates, due to the relative simplicity of these antigenic models, the interpretation of results obtained with them and sometimes permits the detection of differences, such as genetic variations in the capacity to produce specific antibodies (Levine, Ojeda & Benacerraf 1963; McDevitt & Sela 1965), which are not observable with complex natural antigens. Antibodies directed toward synthetic polypeptides may prove useful in studies of the antibody structure and biosynthesis, as it should be possible to correlate differences between the antibodies with the known differences between the synthetic antigens.

scholarly journals Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 863 ◽  
Author(s):  
Artemiy Silantyev ◽  
Luca Falzone ◽  
Massimo Libra ◽  
Olga Gurina ◽  
Karina Kardashova ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Small Molecules ◽  
Current Knowledge ◽  
Analytical Techniques ◽  
Review Article ◽  
Future Trends ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
The Central Nervous System ◽  
Surgical Treatments

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

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