Editing Comparative genomics (section)

=== Sequence alignment ===
[[Sequence alignment|Alignments]] are used to capture information about similar sequences such as ancestry, common evolutionary descent, or common structure and function. Alignments can be done for both nucleotide and protein sequences.<ref>{{cite book | vauthors = Altschul SF, Pop M | chapter = Sequence Alignment |date=2017 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK464187/ | title = Handbook of Discrete and Combinatorial Mathematics | veditors = Rosen KH, Shier DR, Goddard W |edition=2nd |place=Boca Raton (FL) |publisher=CRC Press/Taylor & Francis |isbn=978-1-58488-780-5 |pmid=29206392 |access-date=2022-12-18 }}</ref><ref>{{cite book | vauthors = Prjibelski AD, Korobeynikov AI, Lapidus AL | chapter = Sequence Analysis |date=2019-01-01 | title = Encyclopedia of Bioinformatics and Computational Biology |pages=292–322 | veditors = Ranganathan S, Gribskov M, Nakai K, Schönbach C |place=Oxford |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-809633-8.20106-4 |isbn=978-0-12-811432-2 | s2cid = 226247797 }}</ref> Alignments consist of local or global pairwise alignments, and multiple sequence alignments. One way to find global alignments is to use a dynamic programming algorithm known as [[Needleman–Wunsch algorithm|Needleman-Wunsch algorithm]]<nowiki/>whereas [[Smith–Waterman algorithm]] used to find local alignments. With the exponential growth of sequence databases and the emergence of longer sequences, there's a heightened interest in faster, approximate, or [https://science.umd.edu/labs/delwiche/bsci348s/lec/AlignHeuristic.html#:~:text=Heuristic%20Alignment&text=BLAST%20is%20a%20pairwise%20local,sequence%20databases%20such%20as%20GenBank. heuristic alignment] procedures. Among these, the '''FASTA''' and '''BLAST''' algorithms are prominent for local pairwise alignment. Recent years have witnessed the development of programs tailored to aligning lengthy sequences, such as '''MUMmer''' (1999), '''BLASTZ''' (2003), and '''AVID''' (2003). While BLASTZ adopts a local approach, MUMmer and AVID are geared towards global alignment. To harness the benefits of both local and global alignment approaches, one effective strategy involves integrating them. Initially, a rapid variant of BLAST known as '''BLAT''' is employed to identify homologous "anchor" regions. These anchors are subsequently scrutinized to identify sets exhibiting conserved order and orientation. Such sets of anchors are then subjected to alignment using a global strategy.

Additionally, ongoing efforts focus on optimizing existing algorithms to handle the vast amount of genome sequence data by enhancing their speed. Furthermore, '''MAVID''' stands out as another noteworthy pairwise alignment program specifically designed for aligning multiple genomes.

'''Pairwise Comparison:''' The Pairwise comparison of genomic sequence data is widely utilized in comparative gene prediction. Many studies in comparative functional genomics lean on pairwise comparisons, wherein traits of each gene are compared with traits of other genes across species. his method yields many more comparisons than unique observations, making each comparison dependent on others.<ref>{{cite journal | vauthors = Haubold B, Wiehe T | title = Comparative genomics: methods and applications | journal = Die Naturwissenschaften | volume = 91 | issue = 9 | pages = 405–421 | date = September 2004 | pmid = 15278216 | doi = 10.1007/s00114-004-0542-8 | bibcode = 2004NW.....91..405H }}</ref><ref>{{cite journal | vauthors = Dunn CW, Zapata F, Munro C, Siebert S, Hejnol A | title = Pairwise comparisons across species are problematic when analyzing functional genomic data | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 3 | pages = E409–E417 | date = January 2018 | pmid = 29301966 | pmc = 5776959 | doi = 10.1073/pnas.1707515115 | doi-access = free | bibcode = 2018PNAS..115E.409D }}</ref>

'''Multiple comparisons:''' The comparison of multiple genomes is a natural extension of pairwise inter-specific comparisons. Such comparisons typically aim to identify conserved regions across two phylogenetic scales: 1. Deep comparisons, often referred to as '''phylogenetic footprinting'''<ref>{{cite journal | vauthors = Hardison RC, Oeltjen J, Miller W | title = Long human-mouse sequence alignments reveal novel regulatory elements: a reason to sequence the mouse genome | journal = Genome Research | volume = 7 | issue = 10 | pages = 959–966 | date = October 1997 | pmid = 9331366 | doi = 10.1101/gr.7.10.959 | doi-access = free }}</ref> reveal conservation across higher taxonomic units like vertebrates.<ref>{{cite journal | vauthors = Elgar G, Sandford R, Aparicio S, Macrae A, Venkatesh B, Brenner S | title = Small is beautiful: comparative genomics with the pufferfish (Fugu rubripes) | journal = Trends in Genetics | volume = 12 | issue = 4 | pages = 145–150 | date = April 1996 | pmid = 8901419 | doi = 10.1016/0168-9525(96)10018-4 }}</ref> 2. Shallow comparisons, recently termed 
'''Phylogenetic shadowing''',<ref>{{cite journal |vauthors=Boffelli D, McAuliffe J, Ovcharenko D, Lewis KD, Ovcharenko I, Pachter L, Rubin EM |title=Phylogenetic shadowing of primate sequences to find functional regions of the human genome |journal=Science |volume=299 |issue=5611 |pages=1391–1394 |date=February 2003 |pmid=12610304 |doi=10.1126/science.1081331 |url=https://digital.library.unt.edu/ark:/67531/metadc779156/}}</ref> probe conservation across a group of closely related species. 
[[File:Genomic structural variation.png|thumb|upright=1.15 |Chromosome by chromosome variation of indicine and taurine cattle. The genomic structural differences on chromosome X between indicine (''Bos indicus'' – [[Nelore | Nelore cattle]]) and taurine cattle (''Bos taurus'' – [[Hereford cattle]]) were identified using the SyRI tool.]]