7.3.4 Bioinformatics

• The 21^st Century has seen a tremendous increase in the amount of biological data
  • This has been due to rapid advances in DNA sequencing and other technologies
• Developments in scientific research have been accompanied by improvements in computing, enabling scientists to interpret complex biological data using bioinformatics applications
• Bioinformatics is an interdisciplinary field that develops methods and software to help further our understanding of life by making sense of this data
  • Although many new bioinformatics applications are at the forefront of applied computing, most scientific research uses standard tools and databases
• Data related to gene sequence, protein structure, gene expression or metabolites is curated, annotated and stored in databases such as GenBank, NCBI, EBI, PDB
• A range of open source software tools is available to query this data

Sequence similarity

• If a scientist has an unknown DNA sequence, they can determine if it codes for a gene
• BLAST (Basic Local Alignment Search Tool) search can compare the unknown DNA sequence to all known gene sequences in a particular database
  • BLAST finds regions of similarity between sequences
  • The search returns ‘hits’ which are the sequences most related to the search sequence (depending on the parameters set)
• There are many variations of BLAST that can be used for different analyses such as protein sequences or comparing multiple input sequences at once

Genetic variation and evolutionary relationships

• Scientists can compare homologous gene sequences between many organisms
  • Sequences are compared using an alignment tool such as Clustal W (there are many alternatives)
  • This aligns (stacks) the sequences based on similar regions so that variable regions can be identified
• This determines the degree of similarity between organisms which gives an indication of how closely related the organisms are
  • There may be a common ancestral origin but in some organisms, the gene might have accumulated differences over times from random mutations
• Tree-like evolutionary diagrams (phylogenetic trees) can be constructed with software such as PhyloWin to show the degree of relatedness to a recent common ancestor
• Phylogenetic analysis is useful for biological classification, conservation studies, forensics or molecular epidemiology which can help dictate public health policy
  • Variants of highly infectious pathogens such as SARS-CoV-2 (a well-known coronavirus) can be identified using these techniques

Sequencing DNA to determine protein sequences

• The genetic code can be used to determine the amino acid sequence within a protein
  • This primary structure information can be used to predict how proteins will fold into their tertiary structure
  • This gives a greater level of understanding of how a protein functions or interacts with other proteins or molecules
• Such information can be used for a range of applications, such as drug design or novel protein engineering in synthetic biology