Elevation of plasma tRNA fragments precedes seizures in human epilepsy

Hogg, Marion C.; Raoof, Rana; Naggar, Hany El; Monsefi, Naser; Delanty, Norman; O’Brien, Donncha F.; Bauer, Sebastian; Rosenow, Felix; Henshall, David C.; Prehn, Jochen H.M.

doi:10.1172/jci126346

Cited by 75 publications

(73 citation statements)

References 25 publications

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“…Some studies have reported the effects of circulating tRFs in the diagnosis of epilepsy, clear cell renal cell carcinoma, gastric cancer, and so on. 17,18,28 Most studies directly verified the selected tRFs in tissues or blood, whereas we designed a four-phase study to identify tRFs for the diagnosis of EBC. High-throughput sequencing was applied to identify differentially expressed tRFs and tiRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence indicate that tRFs and tiRNAs have a variety of biological functions, not only related to signal regulation but also involved in various diseases, such as tumors, neurodegenerative diseases, metabolic diseases, and infectious diseases. [14][15][16][17] Recent studies have revealed that tRFs can be found in circulation, indicating that tRFs are potential biomarkers for the diagnosis and prognosis of cancers. 18,19 The aim of this study was to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers for EBC.…”

Section: Introductionmentioning

confidence: 99%

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Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Wang

et al. 2020

Molecular Therapy - Nucleic Acids

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Small RNAs derived from tRNAs are attracting considerable attention; however, the effects of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) as biomarkers have not been investigated in early-stage breast cancer (EBC). The study aimed to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers. The study was conducted in four phases. Thirty tRFs and tiR-NAs were selected by high-throughput sequencing in screening phase and then assessed in training, testing, and external validation phases by qRT-PCR. Six tRFs (tRF-Glu-CTC-003, tRF-Gly-CCC-007, tRF-Gly-CCC-008, tRF-Leu-CAA-003, tRF-Ser-TGA-001, and tRF-Ser-TGA-002) were found significantly downregulated in plasma samples of patients with EBC compared with normal controls, and all were derived from 5 0 ends of tRNAs. Patients with HER2 + EBC with low expression levels of tRF-Glu-CTC-003 were related to worse disease-free survival and overall survival. The identified tRFs were further examined in cell supernatants, exosomes isolated from plasma, and tissues. In conclusion, our study identified six tRFs from the 5 0 ends of tRNAs as novel diagnostic biomarkers for EBC, providing additional evidence for, and a better understanding of, circulating tRFs and EBC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Wang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Although other methods 12 , 20 have given good predictive results (> 90% for some), they are often too complex to process because they can involve significant data processing or t RNA expression analysis. In addition, they are usually invasive, requiring an implant, blood sampling, or the collection of other bodily fluids.…”

Section: Discussionmentioning

confidence: 99%

Prediction and detection of human epileptic seizures based on SIFT-MS chemometric data

Catala¹,

Pagès

Schaff

et al. 2020

Sci Rep

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Although epilepsy is considered a public health issue, the burden imposed by the unpredictability of seizures is mainly borne by the patients. Predicting seizures based on electroencephalography has had mixed success, and the idiosyncratic character of epilepsy makes a single method of detection or prediction for all patients almost impossible. To address this problem, we demonstrate herein that epileptic seizures can not only be detected by global chemometric analysis of data from selected ion flow tube mass spectrometry but also that a simple mathematical model makes it possible to predict these seizures (by up to 4 h 37 min in advance with 92% and 75% of samples correctly classified in training and leave-one-out-cross-validation, respectively). These findings should stimulate the development of non-invasive applications (e.g., electronic nose) for different types of epilepsy and thereby decrease of the unpredictability of epileptic seizures.

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“…The emergence of new animal models of genetic epilepsies provides another opportunity to test detection and seizure interruption strategies in homogeneous models that share some basis with human epilepsy and thus might provide robust data that can be translated to patients harboring these variants. A range of models might stimulate improvements in the low signal to noise ratio in seizure prediction and in the abortion of seizures, such as evaluation of new biomarkers that change prior to seizure initiation 73 and consideration of circadian rhythms. 74 Ultimately, these systems need to be suitable for self-management in the home and other nonmedical settings in order to improve adherence and efficacy.…”

Section: Real-time Management Of Seizuresmentioning

confidence: 99%

Epilepsy Benchmarks Area III: Improved Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects

et al. 2020

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The goals of Epilepsy Benchmark Area III involve identifying areas that are ripe for progress in terms of controlling seizures and patient symptoms in light of the most recent advances in both basic and clinical research. These goals were developed with an emphasis on potential new therapeutic strategies that will reduce seizure burden and improve quality of life for patients with epilepsy. In particular, we continue to support the proposition that a better understanding of how seizures are initiated, propagated, and terminated in different forms of epilepsy is central to enabling new approaches to treatment, including pharmacological as well as surgical and device-oriented approaches. The stubbornly high rate of treatment-resistant epilepsy—one-third of patients—emphasizes the urgent need for new therapeutic strategies, including pharmacological, procedural, device linked, and genetic. The development of new approaches can be advanced by better animal models of seizure initiation that represent salient features of human epilepsy, as well as humanized models such as induced pluripotent stem cells and organoids. The rapid advances in genetic understanding of a subset of epilepsies provide a path to new and direct patient-relevant cellular and animal models, which could catalyze conceptualization of new treatments that may be broadly applicable across multiple forms of epilepsies beyond those arising from variation in a single gene. Remarkable advances in machine learning algorithms and miniaturization of devices and increases in computational power together provide an enhanced opportunity to detect and mitigate seizures in real time via devices that interrupt electrical activity directly or administer effective pharmaceuticals. Each of these potential areas for advance will be discussed in turn.

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Elevation of plasma tRNA fragments precedes seizures in human epilepsy

Cited by 75 publications

References 25 publications

Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

Prediction and detection of human epileptic seizures based on SIFT-MS chemometric data

Epilepsy Benchmarks Area III: Improved Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects

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