My Research is focused on adductomics studies. I work with biological matrixes, e g daphnia, hyalella and amphipods crustaceans living in the Baltic sea, studying the link between biological effects and DNA modifications and working on the association between contaminants, such as metals and PAHs, and DNA modification.

A selection from Stockholm University publication database

• DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

  2023. Giulia Martella (et al.). Environmental Science and Technology 57 (29), 10591-10603

  Article

  Exposure to chemical pollution can induce genetic andepigeneticalterations, developmental changes, and reproductive disorders, leadingto population declines in polluted environments. These effects aretriggered by chemical modifications of DNA nucleobases (DNA adducts)and epigenetic dysregulation. However, linking DNA adducts to thepollution load in situ remains challenging, and thelack of evidence-based DNA adductome response to pollution hampersthe development and application of DNA adducts as biomarkers for environmentalhealth assessment. Here, we provide the first evidence for pollutioneffects on the DNA modifications in wild populations of Baltic sentinelspecies, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screenand characterize genomic DNA modifications was developed, and itsapplicability was demonstrated by profiling DNA modifications in theamphipods collected in areas with varying pollution loads. Then, thecorrelations between adducts and the contaminants level (polycyclicaromatic hydrocarbons (PAHs), trace metals, and pollution indices)in the sediments at the collection sites were evaluated. A total of119 putative adducts were detected, and some (5-me-dC, N-6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNAadductome profiles, including epigenetic modifications, differed betweenthe animals collected in areas with high and low contaminant levels.Furthermore, the correlations between the adducts and PAHs were similaracross the congeners, indicating possible additive effects. Also,high-mass adducts had significantly more positive correlations withPAHs than low-mass adducts. By contrast, correlations between theDNA adducts and trace metals were stronger and more variable thanfor PAHs, indicating metal-specific effects. These associations betweenDNA adducts and environmental contaminants provide a new venue forcharacterizing genome-wide exposure effects in wild populations andapply DNA modifications in the effect-based assessment of chemicalpollution. DNA adductome analysis identifiesexposure to environmentalcontaminants in a sentinel species in the Baltic Sea.

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• DNA adductomics: Method development and integration in biological effect monitoring

  2023. Giulia Martella.

  Thesis (Doc)

  Environmental omics can provide informative biomarkers for identifying pathologies or physiological responses to environmental change. Nucleic acid adductomics, one of the newest omics techniques, is particularly well suited for assessing exposure and effects of environmental contaminants because the technique can capture modifications at the (epi)genome level. However, identifying potential adduct-biomarkers is challenging, especially in non-model organisms. Therefore, the primary aims of this study were to improve the methodology and explore the applicability of nucleic acid adductomics in environmental monitoring of the biological effects of contaminants, using amphipods as sentinel species.

  From a methodology perspective, this thesis presents a gradual progression in screening and detecting DNA modifications. The mass spectrometry (MS) based approach for identifying candidate DNA adducts utilized the characteristic neutral loss of deoxyribose. In Paper I, the data generated from high resolution MS in Full Scan-Data independent Acquisition mode were analyzed manually using the fragmentation pattern of nucleoside adduct ions. In Paper II, processing time and efficiency were significantly improved by the development of nLossFinder software. Further, TraceFinder software was combined and used to evaluate and quantify detected adducts (Paper III). Another important development was a simultaneous approach for analysis of  both DNA and RNA adducts in a single MS run presented in Paper IV. 

  The analysis of amphipod samples based on the existing approaches and methods developed in this thesis showed that reproductive pathologies identified by the microscopic analysis were associated with specific DNA modifications that can be used to classify field-collected individuals according to their health status (Paper I). Moreover, epigenetic marks were the most influential adducts for this classification. Finally, the adduct profile of amphipods differed between the areas with relatively high and low contamination loads based on PAH and trace metal concentrations in the sediment (Paper III). Also, significant correlations were found between DNA adducts and specific contaminants.

  These method developments and findings uniquely contribute to the field of environmental omics, providing tools for data processing and demonstrating the applicability of nucleic acid adductomics in environmental health research and biological effect monitoring.

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• nLossFinder—A Graphical User Interface Program for the Nontargeted Detection of DNA Adducts

  2021. Pedro F.M. Sousa (et al.). Toxics 9 (4)

  Article

  DNA adductomics is a relatively new omics approach aiming to measure known and unknown DNA modifications, called DNA adducts. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. Recent advances in the field of mass spectrometry have allowed the possibility to perform a comprehensive analysis of adducts, for instance, by using a nontargeted data-independent acquisition method, with multiple precursor m/z windows as an inclusion list. However, the generated data are large and complex, and there is a need to develop algorithms to simplify and automate the time-consuming manual analysis that has hitherto been used. Here, a graphical user interface (GUI) program was developed, with the purpose of tracking a characteristic neutral loss reaction from tandem mass spectrometry of the nucleoside adducts. This program, called nLossFinder, was developed in the MATLAB platform, available as open-source code. Calf thymus DNA was used as a model for method optimization, and the overall adductomics approach was applied to DNA from amphipods (Monoporeia affinis) collected within the Swedish National Marine Monitoring Program. In the amphipod DNA, over 150 putative adducts were found in comparison to 18 using a manual approach in a previous study. The developed program can improve the processing time for large MS data, as it processes each sample in a few seconds, and hence can be applicable for high-throughput screening of adducts.

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• DNA epigenetic marks are linked to embryo aberrations in amphipods

  2020. Elena Gorokhova (et al.). Scientific Reports 10

  Article

  Linking exposure to environmental stress factors with diseases is crucial for proposing preventive and regulatory actions. Upon exposure to anthropogenic chemicals, covalent modifications on the genome can drive developmental and reproductive disorders in wild populations, with subsequent effects on the population persistence. Hence, screening of chemical modifications on DNA can be used to provide information on the probability of such disorders in populations of concern. Using a high-resolution mass spectrometry methodology, we identified DNA nucleoside adducts in gravid females of the Baltic amphipods Monoporeia affinis, and linked the adduct profiles to the frequency of embryo malformations in the broods. Twenty-three putative nucleoside adducts were detected in the females and their embryos, and eight modifications were structurally identified using high-resolution accurate mass data. To identify which adducts were significantly associated with embryo malformations, partial least squares regression (PLSR) modelling was applied. The PLSR model yielded three adducts as the key predictors: methylation at two different positions of the DNA (5-methyl-2′-deoxycytidine and N⁶-methyl-2′-deoxyadenosine) representing epigenetic marks, and a structurally unidentified nucleoside adduct. These adducts predicted the elevated frequency of the malformations with a high classification accuracy (84%). To the best of our knowledge, this is the first application of DNA adductomics for identification of contaminant-induced malformations in field-collected animals. The method can be adapted for a broad range of species and evolve as a new omics tool in environmental health assessment.

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• Simultaneous RNA and DNA Adductomics Using Single Data-Independent Acquisition Mass Spectrometry Analysis

  2023. Giulia Martella (et al.). Chemical Research in Toxicology 36 (9), 1471-1482

  Article

  Adductomics studies are used for the detection and characterizationof various chemical modifications (adducts) of nucleic acids and proteins.The advancements in liquid chromatography coupled with high-resolutiontandem mass spectrometry (HRMS/MS) have resulted in efficient methodsfor qualitative and quantitative adductomics. We developed an HRMS-basedmethod for the simultaneous analysis of RNA and DNA adducts in a singlerun and demonstrated its application using Baltic amphipods, usefulsentinels of environmental disturbances, as test organisms. The noveltyof this method is screening for RNA and DNA adducts by a single injectionon an Orbitrap HRMS instrument using full scan and data-independentacquisition. The MS raw files were processed with an open-source program, nLossFinder, to identify and distinguish RNA and DNA adductsbased on the characteristic neutral loss of ribonucleosides and 2 & PRIME;-deoxyribonucleosides,respectively. In the amphipods, in addition to the nearly 150 putativeDNA adducts characterized earlier, we detected 60 putative RNA adducts.For the structural identification of the detected RNA adducts, theMODOMICS database was used. The identified RNA adducts included simplemono- and dimethylation and other larger functional groups on differentribonucleosides and deaminated product inosine. However, 54 of theseRNA adducts are not yet structurally identified, and further workon their characterization may uncover new layers of information relatedto the transcriptome and help understand their biological significance.Considering the susceptibility of nucleic acids to environmental factors,including pollutants, the developed multi-adductomics methodologywith further advancement has the potential to provide biomarkers fordiagnostics of pollution effects in biota.

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Show all publications by Giulia Martella at Stockholm University