Thanatotranscriptome: genes actively expressed after organismal death

Pozhitkov, Alex; Neme, Rafik; Domazet-Lošo, Tomislav; Leroux, B; Soni, Shivani; Tautz, Diethard; Noble, Peter A.

doi:10.1101/058305

Cited by 9 publications

(12 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All probes were calibrated using a dilution series as outlined in our previous studies (18,19,20,21). The Langmuir and Freundlich isotherm equations were fitted to the data and the one with the best fit (R 2 ) was retained.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology

Hunter

Pozhitkov

Noble

2016

Preprint

Self Cite

View full text Add to dashboard Cite

Conceptual models suggest certain microorganisms (e.g., the red complex) are indicative of a specific disease state (e.g., periodontitis); however, recent studies have questioned the validity of these models. Here, the abundances of 500+ microbial species were determined in 16 patients with clinical signs of one of the following oral conditions: periodontitis, established caries, edentulism, and oral health. Our goal was to determine if the abundances of certain microorganisms reflect dysbiosis or a specific clinical condition that could be used as a signature for dental research. Microbial abundances were determined by the analysis of 138,718 calibrated probes using Gene Meter methodology. Each 16S rRNA gene was targeted by an average of 194 unique probes (n=25 nt). The calibration involved diluting pooled gene target samples, hybridizing each dilution to a DNA microarray, and fitting the probe intensities to adsorption models. The fit of the model to the experimental data was used to assess individual and aggregate probe behavior; good fits (R2>0.90) were retained for back-calculating microbial abundances from patient samples. The abundance of a gene was determined from the median of all calibrated individual probes or from the calibrated abundance of all aggregated probes. With the exception of genes with low abundances (< 2 arbitrary units), the abundances determined by the different calibrations were highly correlated (r ∼1.0). Seventeen genera were classified as signatures of dysbiosis because they had significantly higher abundances in patients with periodontitis and edentulism when contrasted with health. Similarly, 13 genera were classified as signatures of periodontitis, and 14 genera were classified as signatures of edentulism. The signatures could be used, individually or in combination, to assess the clinical status of a patient (e.g., evaluating treatments such as antibiotic therapies). Comparisons of the same patient samples revealed high false negatives (45%) for next-generation-sequencing results and low false positives (7%) for Gene Meter results.

show abstract

Section: Resultsmentioning

confidence: 99%

“…18,19). Unlike conventional DNA microarrays, a calibration procedure is conducted prior to applying samples onto the microarrays (20,21). The calibration procedure establishes the microarray probe responses to increasing target concentrations (i.e., a dilution series).…”

Section: Introductionmentioning

confidence: 99%

Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology

Hunter

Pozhitkov

Noble

2016

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nowadays, the most accepted description of death is “permanent cessation of the critical functions of the organism as a whole” (Bernat 1998 ). However, not all the functions cease simultaneously, and the shutdown of a complex biological organism, such as a human being, does not abruptly terminate at time of death (Pozhitkov et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…Not only were these genes active, but they also upregulated or initiated feedback loops including upregulation of immunity, inflammation and cancer genes within one hour from death. It has also been hypothesized by Pozhitkov and colleagues ( 2016 ) that immune reaction against some transplanted organs could be linked to the genetic activity of the organ itself, rather than to immunosuppressive agents (Aberg et al 2008 ; Haagsma et al 2001 ). It was suggested that the risk of suffering a cancer post organ transplantation is associated with pro- oncogenic genes expressed after death (Burra and Rodriguez-Castro 2015 ; Pozhitkov et al 2016 ; Schrem et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has also been hypothesized by Pozhitkov and colleagues ( 2016 ) that immune reaction against some transplanted organs could be linked to the genetic activity of the organ itself, rather than to immunosuppressive agents (Aberg et al 2008 ; Haagsma et al 2001 ). It was suggested that the risk of suffering a cancer post organ transplantation is associated with pro- oncogenic genes expressed after death (Burra and Rodriguez-Castro 2015 ; Pozhitkov et al 2016 ; Schrem et al 2016 ). Increase in transcript abundance after death was attributed to thermodynamics and kinetic dynamics including epigenetic changes (Pozhitkov et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thanatometabolomics: introducing NMR-based metabolomics to identify metabolic biomarkers of the time of death

et al. 2019

View full text Add to dashboard Cite

Introduction Death is the permanent cessation of the critical functions of the organism as a whole. However, the shutdown of a complex biological organism does not abruptly terminate at time of death. New high-throughput technologies allow the systematic investigation of the biochemical modulations occurring after death. Recent genomics studies have demonstrated that genes remain active after death, triggering upregulation of some genes and initiating feedback loops. These genes were mostly involved in pathways related to immunity, inflammation and cancer. These genetic modulations suggest many biochemical events persist after death, which can be captured using a metabolomics approach. Objectives This proof of concept work aimed to determine whether NMR spectroscopy could identify metabolomics changes occurring after death, and characterise the nature of these metabolomics modulations. Methods High-resolution 1 H-NMR spectroscopy was applied to six biological matrices: heart, kidney, liver, spleen, skin and white adipose tissue of ten adult mice at three different type points. Results Forty-three metabolites were associated with post mortem metabolomics modulations. Kidney, heart and spleen showed the highest metabolic perturbations. Conversely, skin and white adipose tissue were the least altered matrices. Early metabolic modulations were associated with energy metabolism and DNA synthesis, by contrast, late metabolomics modulations were associated with microbial metabolism. Conclusions NMR has proven potential to determine the time of death based on post-mortem metabolomics modulations. This could be useful in the context of transplants, forensic studies and as internal quality control in metabolomics studies. Further investigations are required to validate these findings in humans in order to determine which compounds robustly reflect post-mortem metabolic fluctuations to accurately determine the time of death. Electronic supplementary material The online version of this article (10.1007/s11306-019-1498-1) contains supplementary material, which is available to authorized users.

show abstract

Monitoring of post-mortem changes of saliva N-glycosylation by nano LC/MS

et al. 2017

View full text Add to dashboard Cite

The estimation of post-mortem interval (PMI) is a crucial part for investigations of crime and untimely deaths in forensic science. However, standard methods of PMI estimation are easily confounded by extenuating circumstances and/or environmental factors. Therefore, a panel of PMI markers obtained from a more acceptable and accurate method is necessary to definitely determine time of death. Saliva, one of the vital fluids encountered at crime scenes, contains various glycoproteins that are highly affected by biochemical environment. Here, we investigated saliva N-glycans between live and dead rats to determine the alteration of N-glycans using an animal model system because of the limitation of saliva collection from recently deceased humans. Rat saliva samples were collected both before and after death. N-Glycans were enzymatically released by PNGase F without any glycoprotein extraction. Released native glycans were purified and enriched by PGC-SPE. About 100 N-glycans were identified, profiled, and structurally elucidated by nano LC/MS and tandem MS. Sialylated N-glycans were exclusively present in abundance in live rat saliva whereas non-sialylated N-glycans including LacdiNAc disaccharides were detected in high level following death. Through in-depth investigations using quantitative comparison and statistical analysis, 14 N-glycans that significantly changed after death were identified as the potential marker candidates for PMI estimation. To the best of our knowledge, this is the first study to monitor the post-mortem changes of saliva glycosylation, with obvious forensic applications.

show abstract

Thanatotranscriptome: genes actively expressed after organismal death

Cited by 9 publications

References 200 publications

Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology

Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology

Thanatometabolomics: introducing NMR-based metabolomics to identify metabolic biomarkers of the time of death

Monitoring of post-mortem changes of saliva N-glycosylation by nano LC/MS

Contact Info

Product

Resources

About