[Promoting smoking cessation for patients treated by coronary angioplasty at Liege CHU]. / Aide au sevrage tabagique des patients traités par angioplastie coronaire au CHU de Liège.

Smoking cessation appears to be the response that provides the best cost/benefit ratio among cardiovascular prevention actions. However, hospitalization precisely offers a strategic opportunity to initiate smoking cessation. This work evaluates the assistance in smoking cessation of patients treated by coronary angioplasty at the University Hospital of Liege over the last 6 years. It aims to provide food for thought regarding optimal management of smoking. Analysis of data showed a withdrawal rate of 55 % at year one. Strengthening motivation (with motivational interviewing and conversational hypnosis), the use of nicotine replacement and participation in cardiac rehabilitation have been identified as factors in consolidating abstinence. This work attests to the relevance and necessity of the intervention of a tobacco specialist in hospitalization and outpatient settings to ensure follow-up and improve the success rate of smoking cessation.

Le sevrage tabagique apparaît comme la réponse qui permet le meilleur rapport coût/bénéfice parmi les actions de prévention cardiovasculaire. Or, l'hospitalisation offre précisément une opportunité stratégique pour initier l'arrêt du tabagisme. Ce travail évalue l'aide au sevrage tabagique des patients traités par angioplastie coronaire au CHU de Liège durant ces 6 dernières années. Il vise à nourrir la réflexion quant à une prise en charge optimale du tabagisme. L'analyse des données a montré un taux de sevrage de 55 % à un an. Le renforcement de la motivation (avec l'entretien motivationnel et l'hypnose conversationnelle), l'utilisation d'une substitution nicotinique et la participation à la revalidation cardiaque ont été identifiés comme des facteurs de consolidation de l'abstinence. Ce travail atteste de la pertinence et de la nécessité de l'intervention d'un tabacologue en hospitalisation et en ambulatoire pour assurer un suivi et améliorer la réussite du sevrage tabagique.

[Smoking cessation rate after passage in a smoking cessation clinic in patients referred by a respiratory medicine department]. / Taux de sevrage tabagique après prise en charge ambulatoire dans un centre d'aide aux fumeurs (CAF) chez des patients référés par un service de Pneumologie.

Responsible for a significant morbidity and mortality, smoking remains a major public health issue. Smoking cessation clinics are an integral part of the fight against smoking. This retrospective study, carried out between January 2022 and January 2023 on 106 patients who attended the smoking cessation clinics in the Respiratory Department of the University Hospital of Liège, was designed to assess patient cessation rates at 6 months and 1 year, and to identify any factors predicting success or failure. Our data showed a cessation rate of 25 % at 6 months and 19 % at 1 year. Age was slightly more advanced in those who succeeded in smoking cessation at one year (p = 0.05). The obtained cessation rate strongly supports the utility of our smoking cessation clinic for patients wishing to quit smoking.

Responsable d'une morbi-mortalité importante, le tabagisme reste un enjeu, non négligeable, de santé publique. Les consultations d'aide au sevrage font partie intégrante des moyens mis en œuvre pour lutter contre le tabagisme dans une optique de prévention. Cette étude rétrospective, menée entre janvier 2022 et janvier 2023, auprès de 106 patients ayant fréquenté les consultations de tabacologie du Service de Pneumologie du CHU de Liège, avait pour objectifs d'évaluer les taux de sevrage des patients à 6 mois et à 1 an et d'identifier d'éventuels facteurs prédictifs de succès, ou d'échec, au sein de l'échantillonnage étudié. L'analyse des données a démontré un taux de sevrage de 25 % à 6 mois et de 19 % à 1 an. L'analyse des facteurs démographiques montre une moyenne d'âge plus élevée chez les patients qui réussissent leur sevrage à 1 an (p = 0,05). Le taux de sevrage obtenu atteste de la pertinence et de la nécessité de notre accompagnement auprès des patients désireux de cesser de fumer.

A comprehensive assessment of RNA-seq protocols for degraded and low-quantity samples.

BACKGROUND: RNA-sequencing (RNA-seq) has emerged as one of the most sensitive tool for gene expression analysis. Among the library preparation methods available, the standard poly(A) + enrichment provides a comprehensive, detailed, and accurate view of polyadenylated RNAs. However, on samples of suboptimal quality ribosomal RNA depletion and exon capture methods have recently been reported as better alternatives. METHODS: We compared for the first time three commercial Illumina library preparation kits (TruSeq Stranded mRNA, TruSeq Ribo-Zero rRNA Removal, and TruSeq RNA Access) as representatives of these three different approaches using well-established human reference RNA samples from the MAQC/SEQC consortium on a wide range of input amounts (from 100 ng down to 1 ng) and degradation levels (intact, degraded, and highly degraded). RESULTS: We assessed the accuracy of the generated expression values by comparison to gold standard TaqMan qPCR measurements and gained unprecedented insight into the limits of applicability in terms of input quantity and sample quality of each protocol. We found that each protocol generates highly reproducible results (R 2 > 0.92) on intact RNA samples down to input amounts of 10 ng. For degraded RNA samples, Ribo-Zero showed clear performance advantages over the other two protocols as it generated more accurate and better reproducible gene expression results even at very low input amounts such as 1 ng and 2 ng. For highly degraded RNA samples, RNA Access performed best generating reliable data down to 5 ng input. CONCLUSIONS: We found that the ribosomal RNA depletion protocol from Illumina works very well at amounts far below recommendation and over a good range of intact and degraded material. We also infer that the exome-capture protocol (RNA Access, Illumina) performs better than other methods on highly degraded and low amount samples.

Whole genome and exome sequencing reference datasets from a multi-center and cross-platform benchmark study.

With the rapid advancement of sequencing technologies, next generation sequencing (NGS) analysis has been widely applied in cancer genomics research. More recently, NGS has been adopted in clinical oncology to advance personalized medicine. Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from artifacts introduced during NGS processes or data analysis. Therefore, there is an urgent need to develop best practices in cancer mutation detection using NGS and the need for standard reference data sets for systematically measuring accuracy and reproducibility across platforms and methods. Within the SEQC2 consortium context, we established paired tumor-normal reference samples and generated whole-genome (WGS) and whole-exome sequencing (WES) data using sixteen library protocols, seven sequencing platforms at six different centers. We systematically interrogated somatic mutations in the reference samples to identify factors affecting detection reproducibility and accuracy in cancer genomes. These large cross-platform/site WGS and WES datasets using well-characterized reference samples will represent a powerful resource for benchmarking NGS technologies, bioinformatics pipelines, and for the cancer genomics studies.

Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.

Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing.

The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.

High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions.

Due to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small molecules. Using an optimized platform, we provide the relative sensitivities of the heterozygous and homozygous deletion collections for nearly 1800 biologically active compounds. The data quality enables unique insights into pathways that are sensitive and resistant to a given perturbation, as demonstrated with both known and novel compounds. We present examples of novel compounds that inhibit the therapeutically relevant fatty acid synthase and desaturase (Fas1p and Ole1p), and demonstrate how the individual profiles facilitate hypothesis-driven experiments to delineate compound mechanism of action. Importantly, the scale and diversity of tested compounds yields a dataset where the number of modulated pathways approaches saturation. This resource can be used to map novel biological connections, and also identify functions for unannotated genes. We validated hypotheses generated by global two-way hierarchical clustering of profiles for (i) novel compounds with a similar mechanism of action acting upon microtubules or vacuolar ATPases, and (ii) an un-annotated ORF, YIL060w, that plays a role in respiration in the mitochondria. Finally, we identify and characterize background mutations in the widely used yeast deletion collection which should improve the interpretation of past and future screens throughout the community. This comprehensive resource of cellular responses enables the expansion of our understanding of eukaryotic pathway biology.