InterTADs: integration of multi-omics data on topologically associated domains, application to chronic lymphocytic leukemia.
Journal
NAR genomics and bioinformatics
ISSN: 2631-9268
Titre abrégé: NAR Genom Bioinform
Pays: England
ID NLM: 101756213
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
01
07
2021
revised:
21
10
2021
accepted:
13
12
2021
entrez:
20
1
2022
pubmed:
21
1
2022
medline:
21
1
2022
Statut:
epublish
Résumé
The integration of multi-omics data can greatly facilitate the advancement of research in Life Sciences by highlighting new interactions. However, there is currently no widespread procedure for meaningful multi-omics data integration. Here, we present a robust framework, called InterTADs, for integrating multi-omics data derived from the same sample, and considering the chromatin configuration of the genome, i.e. the topologically associating domains (TADs). Following the integration process, statistical analysis highlights the differences between the groups of interest (normal versus cancer cells) relating to (i) independent and (ii) integrated events through TADs. Finally, enrichment analysis using KEGG database, Gene Ontology and transcription factor binding sites and visualization approaches are available. We applied InterTADs to multi-omics datasets from 135 patients with chronic lymphocytic leukemia (CLL) and found that the integration through TADs resulted in a dramatic reduction of heterogeneity compared to individual events. Significant differences for individual events and on TADs level were identified between patients differing in the somatic hypermutation status of the clonotypic immunoglobulin genes, the core biological stratifier in CLL, attesting to the biomedical relevance of InterTADs. In conclusion, our approach suggests a new perspective towards analyzing multi-omics data, by offering reasonable execution time, biological benchmarking and potentially contributing to pattern discovery through TADs.
Identifiants
pubmed: 35047813
doi: 10.1093/nargab/lqab121
pii: lqab121
pmc: PMC8759567
doi:
Types de publication
Journal Article
Langues
eng
Pagination
lqab121Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.
Références
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Biotechniques. 2014 Feb 01;56(2):61-4, 66, 68, passim
pubmed: 24502796
Nat Rev Dis Primers. 2017 Feb 09;3:17008
pubmed: 28179635
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Int J Cancer. 2019 Jun 1;144(11):2695-2706
pubmed: 30447004
Annu Rev Immunol. 2003;21:841-94
pubmed: 12615894
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Science. 2001 Feb 16;291(5507):1304-51
pubmed: 11181995
Protein Sci. 2019 Nov;28(11):1947-1951
pubmed: 31441146
Leukemia. 2015 Feb;29(2):329-36
pubmed: 24943832
Nat Commun. 2020 Feb 5;11(1):735
pubmed: 32024846
Cancer Med. 2018 Nov;7(11):5716-5726
pubmed: 30353687
Haematologica. 2005 Aug;90(8):1078-88
pubmed: 16079107
PLoS Comput Biol. 2013;9(8):e1003118
pubmed: 23950696
Nat Genet. 2019 May;51(5):835-843
pubmed: 31011212
Bioinformatics. 2017 Oct 1;33(19):3088-3090
pubmed: 28575171
Bioinform Biol Insights. 2015 Nov 15;9(Suppl 1):29-46
pubmed: 26609224
Int J Mol Sci. 2017 Feb 15;18(2):
pubmed: 28212287
Brief Bioinform. 2020 Dec 1;21(6):1920-1936
pubmed: 31774481
Haematologica. 2013 Oct;98(10):1487-9
pubmed: 24091925
N Engl J Med. 2000 Dec 28;343(26):1910-6
pubmed: 11136261
Nat Commun. 2019 Aug 9;10(1):3615
pubmed: 31399598
Nat Genet. 2012 Nov;44(11):1236-42
pubmed: 23064414
Nat Genet. 2017 Jan;49(1):65-74
pubmed: 27869826
J Intern Med. 2016 Apr;279(4):347-57
pubmed: 26709197
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Genome Biol. 2014 Feb 20;15(2):R37
pubmed: 24555846
Bioinformatics. 2015 Jan 1;31(1):143-5
pubmed: 25236461
Clin Epigenetics. 2019 Dec 2;11(1):177
pubmed: 31791414
Cell Death Dis. 2017 Jun 22;8(6):e2895
pubmed: 28640249
Blood. 2011 Feb 10;117(6):1781-91
pubmed: 21148333
Nature. 2010 Apr 15;464(7291):993-8
pubmed: 20393554
Int J Lab Hematol. 2020 Jun;42(3):284-291
pubmed: 32083800
Curr Protoc. 2021 Mar;1(3):e90
pubmed: 33780170
Nature. 2015 Oct 22;526(7574):525-30
pubmed: 26466571
Nucleic Acids Res. 2021 Jan 8;49(D1):D325-D334
pubmed: 33290552
Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551
pubmed: 33125081
Nat Commun. 2021 Jan 28;12(1):651
pubmed: 33510161
Epigenetics. 2017 Feb;12(2):113-122
pubmed: 27982725
Contemp Oncol (Pozn). 2015;19(1A):A68-77
pubmed: 25691825
Nat Genet. 2016 Mar;48(3):253-64
pubmed: 26780610
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Clin Epigenetics. 2017 May 30;9:57
pubmed: 28572861
Nature. 2012 Apr 11;485(7398):376-80
pubmed: 22495300
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Haematologica. 2020 Feb 27;105(12):2864-2867
pubmed: 33256389
Blood. 2015 Jul 23;126(4):445-53
pubmed: 26065654
Mol Syst Biol. 2019 May 22;15(5):e8339
pubmed: 31118277
Cell Rep. 2015 Mar 3;10(8):1297-309
pubmed: 25732821
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
J Clin Invest. 1998 Oct 15;102(8):1515-25
pubmed: 9788964
Biol Direct. 2019 Apr 29;14(1):8
pubmed: 31036036
Nature. 2015 Oct 22;526(7574):519-24
pubmed: 26200345
Int J Mol Med. 2007 Oct;20(4):461-9
pubmed: 17786276
Nat Med. 2018 Jun;24(6):868-880
pubmed: 29785028
J Intern Med. 2008 Dec;264(6):549-62
pubmed: 19017179
Blood. 1999 Sep 15;94(6):1848-54
pubmed: 10477713