• Je něco špatně v tomto záznamu ?

Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays

T. Detinis Zur, S. Margalit, J. Jeffet, A. Grunwald, S. Fishman, Z. Tulpová, Y. Michaeli, J. Deek, Y. Ebenstein

. 2025 ; 146 (-) : 103808. [pub] 20250110

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25010032

Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25010032
003      
CZ-PrNML
005      
20250429134920.0
007      
ta
008      
250415e20250110ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.dnarep.2025.103808 $2 doi
035    __
$a (PubMed)39813882
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Detinis Zur, Tahir $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
245    10
$a Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays / $c T. Detinis Zur, S. Margalit, J. Jeffet, A. Grunwald, S. Fishman, Z. Tulpová, Y. Michaeli, J. Deek, Y. Ebenstein
520    9_
$a Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.
650    12
$a toxikogenetika $x přístrojové vybavení $x metody $7 D043922
650    12
$a zobrazení jednotlivé molekuly $x přístrojové vybavení $x metody $7 D000072760
650    12
$a mapování chromozomů $x přístrojové vybavení $x metody $7 D002874
650    12
$a poškození DNA $x genetika $7 D004249
650    12
$a mikrofluidní analytické techniky $x přístrojové vybavení $x metody $7 D046210
650    12
$a nanotechnologie $x přístrojové vybavení $x metody $7 D036103
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a lidé $7 D006801
650    _2
$a oxidační stres $x účinky léků $x genetika $7 D018384
650    _2
$a oprava DNA $x genetika $7 D004260
650    _2
$a regulace genové exprese $7 D005786
650    _2
$a stanovení celkové genové exprese $7 D020869
650    _2
$a variabilita počtu kopií segmentů DNA $7 D056915
650    _2
$a bromičnany $x toxicita $7 D001959
655    _2
$a časopisecké články $7 D016428
700    1_
$a Margalit, Sapir $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Jeffet, Jonathan $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; School of Physics and Astronomy, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Grunwald, Assaf $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Fishman, Sivan $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Tulpová, Zuzana $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Institute of Experimental Botany of the Czech Academy of Sciences, Olomouc, Czech Republic
700    1_
$a Michaeli, Yael $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Deek, Jasline $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
700    1_
$a Ebenstein, Yuval $u School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 6997801, Israel; Department of Biomedical Engineering, Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: uv@tauex.tau.ac.il
773    0_
$w MED00006619 $t DNA repair $x 1568-7856 $g Roč. 146 (20250110), s. 103808
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39813882 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250415 $b ABA008
991    __
$a 20250429134915 $b ABA008
999    __
$a ok $b bmc $g 2311415 $s 1247113
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2025 $b 146 $c - $d 103808 $e 20250110 $i 1568-7856 $m DNA repair $n DNA Repair (Amst) $x MED00006619
LZP    __
$a Pubmed-20250415

Najít záznam

Citační ukazatele

Možnosti archivace