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Gentle Masking of Low-Complexity Sequences Improves Homology Search

Publication Date: December 19, 2011
Journal: PLOS ONE
Author: Martin C. Frith
Volume: 6
Issue: 12
Pages: e28819
DOI: https://dx.plos.org/10.1371/journal.pone.0028819
Publisher URL: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0028819
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/22205972
PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242753
Europe PMC: http://europepmc.org/abstract/MED/22205972
Web of Science: 000298665600008
Scopus: 83655198251
Mendeley: http://www.mendeley.com/research/gentle-masking-lowcomplexity-sequences-improves-homology-search

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{"title"=>"Gentle masking of low-complexity sequences improves homology search", "type"=>"journal", "authors"=>[{"first_name"=>"Martin C.", "last_name"=>"Frith", "scopus_author_id"=>"13407194500"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"83655198251", "doi"=>"10.1371/journal.pone.0028819", "pui"=>"363105765", "pmid"=>"22205972", "scopus"=>"2-s2.0-83655198251", "issn"=>"19326203"}, "id"=>"2e3a88e4-dd95-3b20-9a95-dc6acea3aaba", "abstract"=>"Detection of sequences that are homologous, i.e. descended from a common ancestor, is a fundamental task in computational biology. This task is confounded by low-complexity tracts (such as atatatatatat), which arise frequently and independently, causing strong similarities that are not homologies. There has been much research on identifying low-complexity tracts, but little research on how to treat them during homology search. We propose to find homologies by aligning sequences with \"gentle\" masking of low-complexity tracts. Gentle masking means that the match score involving a masked letter is min(0,S), where S is the unmasked score. Gentle masking slightly but noticeably improves the sensitivity of homology search (compared to \"harsh\" masking), without harming specificity. We show examples in three useful homology search problems: detection of NUMTs (nuclear copies of mitochondrial DNA), recruitment of metagenomic DNA reads to reference genomes, and pseudogene detection. Gentle masking is currently the best way to treat low-complexity tracts during homology search.", "link"=>"http://www.mendeley.com/research/gentle-masking-lowcomplexity-sequences-improves-homology-search", "reader_count"=>36, "reader_count_by_academic_status"=>{"Researcher"=>7, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>7, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>22, "Medicine and Dentistry"=>1, "Computer Science"=>8}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Computer Science"=>{"Computer Science"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "United Kingdom"=>1, "France"=>2}, "group_count"=>1}

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Figshare08 Jan 06:22 UTC

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{"files"=>["https://ndownloader.figshare.com/files/700706"], "description"=>"The upper sequence is the DNA read “1_lane2_104963”; the lower sequence is from the genome “A1-86”. Lowercase red letters were masked by tantan.", "links"=>[], "tags"=>["metagenomic", "dna", "aligned", "bacterial"], "article_id"=>371089, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_metagenomic_DNA_read_aligned_to_a_bacterial_genome_/371089", "title"=>"A metagenomic DNA read aligned to a bacterial genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:37:33"}
{"files"=>["https://ndownloader.figshare.com/files/700778"], "description"=>"This shows two local alignments between a protein (Q494U1, upper sequence) and human chromosome 1 (lower sequence). Lowercase red letters were masked by tantan. The upper alignment was found with gentle masking, but not with harsh masking.", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>371166, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignments_between_a_protein_and_the_human_genome_/371166", "title"=>"Alignments between a protein and the human genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:37:56"}
{"files"=>["https://ndownloader.figshare.com/files/700834"], "description"=>"This shows alignments between: (A) the C. elegans genome and the reversed P. pacificus genome; (B) the A. thaliana genome and the reversed P. patens genome; (C) vertebrate proteins and reversed plant proteins; (D) the human genome and the reversed opossum genome; (E) the P. falciparum genome and the reversed D. discoideum genome; (F) the P. falciparum genome and the reversed human genome. The colors indicate alignments after: masking both sets of sequences (solid red); masking the first-named set only (dotted magenta); masking the second-named set only (dashed blue); shuffling the letters in each set (dashed brown). The black lines indicate the expected number of alignments for random sequences.", "links"=>[], "tags"=>["reversed"], "article_id"=>371232, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignments_of_reversed_sequences_with_gentle_masking_/371232", "title"=>"Alignments of reversed sequences, with gentle masking.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:38:14"}
{"files"=>["https://ndownloader.figshare.com/files/700963"], "description"=>"Alignments between: (A) the C. elegans genome and the reversed P. pacificus genome; (B) the A. thaliana genome and the reversed P. patens genome; (C) the human genome and the reversed opossum genome. The colors indicate alignments after: masking both sets of sequences (solid red); masking the first-named set only (dotted magenta); masking the second-named set only (dashed blue); shuffling the letters in each set (dashed brown). The black lines indicate the expected number of alignments for random sequences.", "links"=>[], "tags"=>["reversed", "hoxd70", "scoring"], "article_id"=>371345, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignments_of_reversed_sequences_using_the_HOXD70_scoring_scheme_/371345", "title"=>"Alignments of reversed sequences, using the HOXD70 scoring scheme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:38:47"}
{"files"=>["https://ndownloader.figshare.com/files/701038"], "description"=>"This shows alignments between: (A) the C. elegans genome and reversed plant proteins; (B) the P. falciparum genome and reversed vertebrate proteins. The colors indicate alignments after: masking the proteins, and the DNA at the protein level (solid red); masking the proteins, and the DNA at the DNA level (solid blue); masking the proteins only (dashed red); masking the DNA only, at the DNA level (dashed blue); shuffling the letters in each set (dashed brown). The black lines indicate the expected number of alignments for random sequences.", "links"=>[], "tags"=>["dna", "sequences", "reversed"], "article_id"=>371430, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignments_between_DNA_sequences_and_reversed_protein_sequences_with_gentle_masking_/371430", "title"=>"Alignments between DNA sequences and reversed protein sequences, with gentle masking.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:39:12"}
{"files"=>["https://ndownloader.figshare.com/files/701091"], "description"=>"This kind of nonsensical alignment may occur if masked letters (lowercase red) always receive a score of 0.", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>371475, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignment_problem_using_a_mask_score_of_0_/371475", "title"=>"Alignment problem using a mask score of 0.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:39:28"}
{"files"=>["https://ndownloader.figshare.com/files/701128"], "description"=>"(A) An alignment that is significant when scored with blosum80 but not blosum62. (B) Two local alignments between a protein (Q9BZQ4, upper sequence) and human chromosome 1 (lower sequence). The blue arrowheads indicate spurious over-extension of the second alignment. This over-extension occurs when the blosum62 matrix is used for alignment, but not when blosum80 is used. (Actually, it is conceivable that the extension correctly indicates homology: the genomic segment marked by blue arrowheads could be paralogous to the genomic segment in the first alignment.)", "links"=>[], "tags"=>["blosum80"], "article_id"=>371513, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignments_using_BLOSUM80_or_BLOSUM62_/371513", "title"=>"Alignments using BLOSUM80 or BLOSUM62.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 10:39:42"}
{"files"=>["https://ndownloader.figshare.com/files/701169"], "description"=>"Example of an enlarged score matrix for gentle masking.", "links"=>[], "tags"=>["enlarged", "matrix"], "article_id"=>371559, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Example_of_an_enlarged_score_matrix_for_gentle_masking_/371559", "title"=>"Example of an enlarged score matrix for gentle masking.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 10:39:53"}
{"files"=>["https://ndownloader.figshare.com/files/701201"], "description"=>"NUMTs found with gentle or harsh masking.", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>371588, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Martin C. Frith"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028819.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NUMTs_found_with_gentle_or_harsh_masking_/371588", "title"=>"NUMTs found with gentle or harsh masking.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 10:40:02"}

PMC Usage Stats 137117 Jan 16:08 UTC

PMC Usage Stats | Further Information

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Relative Metric 20716510 May 16:34 UTC

Relative Metric

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F1000Prime20 Jan 12:33 UTC

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