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Given the substantial chemical energy and harmful pollutants stored in refining wastewater (RW), energy recovery from RW has emerged as a promising strategy to address both energy scarcity and environmental degradation. In this study, we constructed a microbial fuel cell (MFC) facilitated by an electroactive microbial community to harness energy from RW. After the treatment of RW by MFC, high efficient removal rates of chemical oxygen demand (89.76%), NH 4 +-N (61.78%), total phosphorus (78.38%), chroma (81.53%), and turbidity (86.57%) were achieved. During the treatment of RW, the MFC system produced a maximum output voltage of 347 mV and a maximum power density of 337 mW m−2. High-throughput sequencing analysis revealed that the dominant phylum of domesticated microbial community was Proteobacteria (97.66%) and the dominant class was Gammaproteobacteria (70.10%). Furthermore, three dominant exoelectrogens (Paraburkholderia fungorum YS95, Pseudomonas sp. YS, and Stenotrophomonas maltophilia XS) capable of extracellular electron transfer were identified from the anodic samples. Notably, P. fungorum YS95 was identified as a novel exoelectrogen with significant naphthalene degradation capability. These results highlight the MFCs' efficiency in treating RW and recovering energy, with the discovery of exoelectrogens revealing the untapped potential for energy recovery from petroleum hydrocarbon pollutants. [Display omitted] • Refining wastewater treatment was achieved in MFC with 89.76% COD removal rate. • Energy recovery from refining wastewater was obtained with high power density. • Three dominant exoelectrogens were identified based on high-throughput sequencing. • A green alternative for energy recovery from refining wastewater was established. [ABSTRACT FROM AUTHOR]

Gut single-cell eukaryotes (GSCEs) are residents of billions of people, yet their roles in gut ecology remain largely unknown. Understanding GSCEs is crucial to avoiding misguided eradication efforts that could disrupt gut microbiome homeostasis. Retrospective analyses suggest links between GSCEs, gut bacteria, and host health, but expose methodological pitfalls. Current methods for studying GSCEs are underdeveloped, accentuating the need for more reference genomes and improved bioinformatic pipelines. Blastocystis is often studied in isolation, which comes with a risk of misattributing effects that could be due to other GSCEs. Gut single-celled eukaryotes (GSCEs) are found in billions of people worldwide, but we still know little about their functions and relationships in human gut ecology. Lately, retrospective analysis of bacterial data obtained by next-generation sequencing (NGS) methods has been used to identify links between GSCEs, gut bacteria, host metabolism, and host phenotypical traits, suggesting possible direct or indirect associations to favorable gut microbiome features and other health parameters. Here, we highlight some of the pitfalls related to the research strategy typically used so far and propose action points that could pave the way for a more accurate understanding of GSCEs in human health and disease. [ABSTRACT FROM AUTHOR]

The boundary between polygenic and monogenic diabetes is less distinct than previously believed, with oligogenic forms providing a bridge between these forms. The advent of large-scale next-generation sequencing has enabled the identification of rare variants in several genes causing oligogenic type 2 diabetes. Identification of these rare oligogenic variants has been achieved through two primary approaches: targeted studies of candidate genes enhanced by functional analyses, and large-scale exome- or genome-wide sequencing studies. The demarcation between monogenic and polygenic type 2 diabetes (T2D) is less distinct than previously believed. Notably, recent research has highlighted a new entity, that we suggest calling oligogenic forms of T2D, serving as a genetic link between these two forms. In this opinion article, we have reviewed scientific advances that suggest categorizing genes involved in oligogenic T2D. Research focused on polygenic T2D has faced challenges in deepening our comprehension of the pathophysiology of T2D due to the inability to directly establish causal links between a signal and the molecular mechanisms underlying the disease. However, the study of oligogenic forms of T2D has illuminated distinct causal connections between genes and disease risk, thereby indicating potential new drug targets. [ABSTRACT FROM AUTHOR]

Cryptic MHC-associated peptides (MAPs) originate from various genomic elements that generate short, rapidly degraded polypeptides that are very efficient substrates for MHC I processing. The systematic exploration of the cryptic immunopeptidome is best achieved by integrating RNA-Seq, Ribo-Seq, and mass spectrometry analyses. In several cancer types, most tumor-specific antigens are cryptic MAPs resulting from epigenetic changes and splicing aberrations. Transposable elements are genetic parasites that contribute to the cryptic immunopeptidome and regulate thymic development and function. They are highly expressed in thymic medullary cells, crucial for establishing self-tolerance. Viruses generate cryptic MAPs that can be highly immunogenic and should be considered when designing RNA vaccines. Peptides presented by MHC proteins regulate all aspects of T cell biology. These MHC-associated peptides (MAPs) form what is known as the immunopeptidome and their comprehensive analysis has catalyzed the burgeoning field of immunopeptidomics. Advances in mass spectrometry (MS) and next-generation sequencing have facilitated significant breakthroughs in this area, some of which are highlighted in this article on the cryptic immunopeptidome. Here, 'cryptic' refers to peptides and proteins encoded by noncanonical open reading frames (ORFs). Cryptic MAPs derive mainly from short unstable proteins found in normal, infected, and neoplastic cells. Cryptic MAPs show minimal overlap with cryptic proteins found in whole-cell extracts. In many cancer types, most cancer-specific MAPs are cryptic. [ABSTRACT FROM AUTHOR]

A recent trend in some wineries is the return to using spontaneous fermentation, but it is not clear whether winery flora or vineyard microorganisms drive fermentation. We compared fungal communities during the spontaneous fermentation of wine produced in a winery and in a laboratory with sterilized equipment using three grape cultivars (Chardonnay, Merlot, and Muscat Bailey A) obtained from the same harvest. High-throughput sequencing analysis based on the ITS1 region showed that Saccharomyces cerevisiae was the dominant species in winery batches at the end of fermentation, but it was not always dominant in laboratory batches. The number of laboratory batches where S. cerevisiae reached more than 50% at the end of fermentation was only 10 of 26. Consistent with this, in the grape juice/must before fermentation, S. cerevisiae accounted for 1.71% of fungal species identified in winery batches and 0.04% in laboratory batches. In addition, in laboratory-based winemaking, juice clarification of Chardonnay and cold maceration of Merlot influenced the microbial communities observed during fermentation. Our findings suggest that S. cerevisiae present in the winery environment participates at an early stage of fermentation, leading to its dominance at the end in wine produced by spontaneous fermentation in a winery. • Fungal community was compared between winery and laboratory spontaneous fermentation. • In winery fermentations, Saccharomyces cerevisiae ultimately became dominant. • In laboratory fermentations, S. cerevisiae was not always the dominant species. • S. cerevisiae present in the winery environment seems to participate in fermentation. • Conditions such as juice clarification affect microbial communities in fermentation. [ABSTRACT FROM AUTHOR]

Cell-free DNA to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cell-free DNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of Rhesus immune globulin were conserved. Recently 2 U.S. companies have introduced cell-free DNA assays for RHD as part of their noninvasive prenatal testing assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-D s genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM has recently announced a national shortage. Given the current availability of reliable cell-free DNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S. [ABSTRACT FROM AUTHOR]

• Neoplasms with positive results for TMB/MSI are highly concordant with positive dMMR results. • Genetic/epigenetic alterations in the MMR genes are the main underlying reason for positive TMB/MSI findings. • Association of loss of MSH2/MSH6 IHC with prostatic carcinoma is interesting, but our sample size is limited. Further studies are warranted. Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI). In this single center, retrospective study, our primary aim was to assess if NGS-based positive TMB/MSI findings are concordant with patient matched concurrent MMR IHC studies. In addition, we determined if positive TMB/MSI findings are attributable to genetic/epigenetic alterations of MMR genes. Finally, we explored potential associations between IHC, TMB and MSI findings and specific tumor types We screened 4,258 patients in our database who had tumor-normal-testing with our institutional high-throughput NGS-based CLIA assay between Apr 1, 2021-August 31, 2022 for TMB and MSI. We identified 65 patients who had neoplasms with documented TMB-High/MSI-High (n = 59) or TMB-High/MSI-Undetermined (n = 6) results as well as concurrent IHC results for MMR proteins [colorectal (n = 25), endometrial (n = 28), prostatic (n = 7), urothelial (n = 3), other (n = 5)]. The concordance between positive NGS TMB/MSI and MMR results was 98 %. Genetic/epigenetic alterations of MMR genes were documented in 78 % of the neoplasms. IHC studies for dMMR proteins revealed loss of MLH1/PMS2 (n = 33), MSH2/MSH6 (n = 14), MLH1/MSH2/PMS2 (n = 1), MLH1 (n = 1), MSH2 (n = 2), MSH6 (n = 6) and PMS2 (n = 6). All six prostatic neoplasms with dMMR had loss of MSH2/MSH6 (p < 0.0001). We conclude that neoplasms with positive results for TMB/MSI are highly concordant with positive dMMR results. Genetic/epigenetic alterations in the MMR genes are an underlying reason for most positive findings. The association of MSH2/MSH6 loss with prostatic neoplasms is of in-terest, but sample size is limited, and further studies are warranted to address this association [ABSTRACT FROM AUTHOR]

• Some limited studies have indicated a correlation between driver gene mutations and organ-specific metastasis. Our research tried to expore the genomic characteristics and molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. • EGFR mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant less enrichment in the adrenal metastases (AM) group (P <0.001). • ALK mutations in the AM group correlated with shorter overall survival (P <0.001). KRAS mutations in the early synchronous adrenal metastases group were also associated with shorter OS (P <0.001). The aim of this study was to examine the genomic characteristics and explore the molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. 57 patients diagnosed with lung adenocarcinoma (LUAD) and adrenal metastases (AM) were enrolled, alongside 33 controls diagnosed with non-adrenal metastases (non-AM) at the time of diagnosis. The primary lung cancer tissue sample were analyzed using next-generation sequencing. The molecular and clinical features were correlated with clinical outcomes. TP53, EGFR and KRAS were the most frequently mutated gene in both groups. EGFR mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant enrichment in the non-AM group (P <0.001). An elevated age-related signature in the group of patients with AM, whereas the non-AM group exhibited a higher BRCA signature. Potential prognostic biomarkers such as KEAP1, LRP1B, NOTCH1 and RET mutations were detected in the non-AM group, while ALK mutations in the AM group correlated with shorter overall survival (P <0.001). KRAS mutations in the early synchronous adrenal metastases group were also associated with shorter OS (P <0.001). The analysis of 425 tumor genes in 29 patients with adrenal metastases showed significant enrichment in pathways associated with invasion and metastasis, including TNF signaling pathway and TGF-β signaling pathway. Patients without EGFR mutations in LUAD need to be more concerned about adrenal metastases. Meanwhile, patients with adrenal metastases harboring ALK or KRAS mutations have a poor prognosis and require more aggressive treatment. The TNF and TGF-β pathways might be associated with adrenal metastasis. [ABSTRACT FROM AUTHOR]

In rice fields, rice plants usually grow alongside wild weeds and are attacked by various invertebrate species. Viruses are abundant in plants and invertebrates, playing crucial ecological roles in controlling microbial abundance and maintaining community structures. To date, only 16 rice viruses have been documented in rice-growing regions. These viruses pose serious threats to rice production and have traditionally been identified only from rice plants and insect vectors by isolation techniques. Advances in next-generation sequencing (NGS) have made it feasible to discover viruses on a global scale. Recently, numerous viruses have been identified in plants and invertebrates using NGS technologies. In this review, we discuss viral studies in rice plants, invertebrate species, and weeds in rice fields. Many novel viruses have been discovered in rice ecosystems through NGS technologies, with some also detected using metatranscriptomic and small RNA sequencing. These analyses greatly expand our understanding of viruses in rice fields and provide valuable insights for developing efficient strategies to manage insect pests and virus-mediated rice diseases. [ABSTRACT FROM AUTHOR]

• The embryonic factor is key to success in ART infertility treatment. • PGT boosts ART effectiveness, raising live birth rates by 1.5 times. • Implantation window timing aids in improving IVF outcomes. • Personalized embryo transfer and PGT boost RIF patient outcomes by 3.4 times. When a high-quality embryo is implanted into the uterus, but the pregnancy is not established as shown by the ultrasound visualization of an intrauterine gestational sac, this is known as "implantation failure." Cases when more than two times implantation failure occurred was defined as recurrent implantation failure (RIF). Additional testing is done at this stage of infertility treatment to avoid a repeat of the same result with a future in vitro fertilization (IVF) effort. The study aimed to evaluate predictive value of using embryo transfer personalization because of the implantation window study in combination with preimplantation genetic testing in patients with recurrent implantation attempts. Briefly describe the main methods or treatments applied: Ninety-three infertile women make up the sample for this prospective cohort study. In regard to treatment results, the study intends to assess the predictive importance of patient characteristics, screening indicators, and several features of IVF cycles, such as the quantity, quality, and developmental stage of the transferred embryos. Statistical methods employed include the calculation of the median (Me) and interquartile range (IQR) for continuous variables. The Mann-Whitney U test was used to discern differences between unrelated samples, while categorical variables were presented as absolute and percentage values. The Pearson's Chi-squared test assessed differences between groups. Logistic regression, utilizing both enter and backward Wald methods, was applied to establish associations with binary outcomes. The integration of individualized embryo transfer and preimplantation genetic testing (PGT) significantly enhanced the likelihood of live births by 3.4 times in patients experiencing recurrent implantation failure (RIF), with a statistical significance of p = 0.026. In contrast, employing PGT alone increased the probability of live births by 1.5 times; however, this result was not statistically significant (p = 0.439). The predictive model for live birth in patients with RIF, based on our study findings, is defined as follows: the probability of live birth = 1.936 + [1.014 if PGT-A embryos are utilized for transfer] + [1.742 if endometrial preparation is tailored according to the Wellbeing Index (WI)] − [1.860 in cases of secondary infertility] − [1.891 when a male factor is involved]. The determination of the implantation window (IW) and PGT of the embryo are efficient methods of live birth achievement for patients with RIF. [ABSTRACT FROM AUTHOR]

RNU4 - 2 is a newly identified, noncoding gene responsible for a significant proportion of individuals with neurodevelopmental disorders (NDDs). Diagnosis is hampered by the inability of commonly employed clinical testing methods, including exome sequencing and currently formulated multigene panels, to detect variants in the noncoding region. The relatively high prevalence of this condition, predicted to affect thousands of undiagnosed children with NDDs, makes it even more relevant to have better tools to facilitate diagnosis. The initial report of the gene-disease association outlined aggregate phenotypic features but lacked detailed patient evaluations, potentially under-reporting phenotypic features and failing to highlight unique aspects. We aimed to identify individuals with RNU4 - 2 gene variants to deeply phenotype the clinical profile. We sought to define key features that may suggest the diagnosis, to highlight individuals for whom specialized testing, able to detect noncoding region variants, may be indicated. We reviewed genomic data from 6,734 individuals, identifying five with recurrent de novo RNU4 - 2 (n.64_65insT) variants. We clinically evaluated four. Findings were compared with those previously reported. We identify common clinical features, a distinctive dysmorphic facial pattern, and shared imaging abnormalities. We describe novel aspects including longitudinal trajectory and treatment response. Enhanced recognition of the RNU4 - 2 (n.64_65insT-common variant) phenotype, particularly the dysmorphic facial features, will facilitate earlier diagnosis. Distinctive characteristics will guide the selection of patients for testing able to detect RNU4 - 2 variants: genome sequencing or targeted gene testing. Furthermore, health and research systems may identify undiagnosed patients by querying databases for individuals exhibiting the traits described herein. [ABSTRACT FROM AUTHOR]

This study aimed to explore the clinical utility of targeted MECP2 testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria. Eligible participants with global developmental delay/arrest or regression before age 36 months underwent MECP2 testing. MECP2 -positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age. Of the 683 patients, 162 (23.7%) were diagnosed with MECP2 -related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of MECP2 testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing. Targeted MECP2 testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted MECP2 testing in younger patients without typical RTT features. [ABSTRACT FROM AUTHOR]

Amplicon-based next-generation sequencing (NGS) of ribosomal genes (metabarcoding) takes advantage of the fact that such genes (16S and 18S in prokaryotes and eukaryotes, respectively) are present in all nonviral organisms and are potent taxonomic markers – particularly for gut protozoa. Although metabarcoding applied to faecal DNA may not be a method that can be used diagnostically to rule out infection, it is a cost-effective screening tool that can provide detailed insight into gut microbiota diversity even at species/subtype level. Metabarcoding bypasses the limitations of traditional Sanger sequencing by enabling insight into intra-species genetic diversity and the delineation of mixed species/subtype infection. Coupled with knowledge on host specificity, a metabarcoding-generated taxonomic 16S+18S profile of a given faecal sample can largely identify the host from which it came. Next-generation sequencing (NGS) methods include whole-genome sequencing, metagenomic analysis, and amplicon-based NGS, all of which are gaining territory in parasitology. A modality of particular interest within the field of gut protozoology is exhaustive metabarcoding of ribosomal genes in a complex matrix such as faeces, by which method, amplicon-based NGS enables the detection and differentiation of both eukaryotic and prokaryotic organisms, circumventing Sanger sequencing-based limitations and representing a one-fits-most approach. Apart from being a tool to break the code of intracellular genetic variation and tell mixed species infections apart, metabarcoding can produce data that can serve to augment our understanding of the interplay between the organisms within the gut. [ABSTRACT FROM AUTHOR]

Olmsted syndrome (OS) is a rare genodermatosis predominantly inherited in an autosomal dominant manner, typically arising from gain-of-function (GOF) variants in the transient receptor potential channel vanilloid 3 (TRPV3) gene. This study aims to investigate potential mechanisms underlying OS in two cases presenting with an autosomal recessive inheritance pattern. Next-generation sequencing panel was employed to identify TRPV3 variants. TRPV3 plasmids carrying specific point variations were generated and transiently transfected into HEK293T cells. Electrophysiological patch-clamp techniques were utilized to record voltage-activated and ligand-activated currents. Celltiter-Glo luminescent assay was employed to analyze the cell viabilities. Compound heterozygous variants, c.1563 G>C (p.W521C) and c.1376 C>T (p.S459L), as well as c.1773 G>C (p.L591F) and c.2186 G>A (p.R729Q), were identified in the two OS patients respectively. Electrophysiological analysis of ligand-induced activation of TRPV3 variants demonstrated the closest correlation with clinical manifestations. All four variants displayed GOF channel activity characterized by increased sensitivity. Notably, W521C and L591F exhibited both heightened sensitivity and lower EC50 values for the TRPV3 agonist. Co-transfection with wild-type TRPV3 plasmids significantly rescued these effects. Cells co-transfected with the corresponding compound heterozygous variants exhibited intermediate electrophysiological characteristics. In this study, we present two cases of OS by autosomal-recessive inheritance of TPRV3 variants. This study presents a notable observation of compound heterozygous GOF variants in TRPV3 , highlighting their cumulative impact on clinical manifestations. Additionally, we advocate for the use of ligand-dependent ion channel activity assays to assess the pathogenicity of TRPV3 variants in OS. • Compound heterozygous GOF variants in TRPV3 were identified in two cases of OS. • The pathogenicity of GOF variants in the TRPV3 gene has a certain threshold. • Biallelic GOF TRPV3 variants result in an additive effect on channel activity. • Using ligand-dependent electrophysiological assays to assess the pathogenicity. [ABSTRACT FROM AUTHOR]

A comprehensive analysis of the microbiome and volatile organic compounds (VOC) in the moromi of soy sauce during fermentation and aging was conducted under industrial production. Microbiome analysis using next-generation sequencing revealed the presence and dynamics of microorganisms other than Aspergillus , Tetragenococcus , Zygosaccharomyces , and Wickerhamiella , which were used as starters. The bacterial community of the moromi on the first day of this process was rich in diversity. Staphylococcus , Bacillus , Kurthia , Acinetobacter , Enterococcus , and Macrococcus that grew during koji making were relatively dominant. However, as the fermentation progressed, only Tetragenococcus became dominant in the bacterial communities. In contrast, the fungal community was simple at the beginning of fermentation and aging, with Aspergillus present almost exclusively. After adding Zygosaccharomyces rouxii on day 42, the fungal community changed significantly. At the end of fermentation and aging, the fungal community diversified, with Millerozyma , Wickerhamiella , Yamadazyma , and Saccharomycopsis becoming dominant. The analysis of VOC showed that the VOC profile changed during fermentation and aging, and that the VOC profile changed significantly after adding Z. rouxii. The correlation analysis between the microbiome and VOC showed that Wickerhamiella , Millerozyma , Debaryomyces , Yamadazyma , and Candida had a significant positive correlation with alcohols, esters, and phenols produced in the later stage of fermentation and aging, indicating that not only Z. rouxii but also various fungi may contribute to the formation of the complex aroma profile of soy sauce. [ABSTRACT FROM AUTHOR]

The reader will gain an improved understanding of: • Key terminology used in microbiome research for respiratory paediatrician. • The methods used to investigate microbial communities in the lungs, including their advantages and limitations. • Differences in the development of lung microbiota in preterm and term infants. • Associations between lung microbiota in chronic lung disease in children and the contribution role of oral taxa in disease. • The gut-lung axis. The advent of next generation sequencing has rapidly challenged the paediatric respiratory physician's understanding of lung microbiology and the role of the lung microbiome in host health and disease. In particular, the role of "microbial key players" in paediatric respiratory disease is yet to be fully explained. Accurate profiling of the lung microbiome in children is challenging since the ability to obtain lower airway samples coupled with processing "low-biomass specimens" are both technically difficult. Many studies provide conflicting results. Early microbiota-host relationships may be predictive of the development of chronic respiratory disease but attempts to correlate lower airway microbiota in premature infants and risk of developing bronchopulmonary dysplasia (BPD) have produced mixed results. There are differences in lung microbiota in asthma and cystic fibrosis (CF). The increased abundance of oral taxa in the lungs may (or may not) promote disease processes in asthma and CF. In CF, correlation between microbiota diversity and respiratory decline is commonly observed. When one considers other pathogens beyond the bacterial kingdom, the contribution and interplay of fungi and viruses within the lung microbiome further increase complexity. Similarly, the interaction between microbial communities in different body sites, such as the gut-lung axis, and the influence of environmental factors, including diet, make the co-existence of host and microbes ever more complicated. Future, multi-omics approaches may help uncover novel microbiome-based biomarkers and therapeutic targets in respiratory disease and explain how we can live in harmony with our microbial companions. [ABSTRACT FROM AUTHOR]

As an energy and carbon saving process for nitrogen removal from wastewater, the partial nitrification and denitrification process (PN/D) has been extensively researched. However, achieving stable PN in municipal wastewater has always been challenging. In this study, a gel immobilized PN/D nitrogen removal process (GI-PN/D) was established. A 94 days pilot-scale experiment was conducted using real municipal wastewater with an ammonia concentration of 43.5 ± 5.3 mg N/L at a temperature range of 11.3–28.7℃. The nitrogen removal performance and associated pathways, shifts in the microbial community as well as sludge yield were investigated. The results were as follows: the effluent TN and COD were 0.6 ± 0.4 mg/L and 31.1 ± 3.8 mg/L respectively, and the NAR exceeding 95%. GI-PN/D achieved deep nitrogen removal of municipal wastewater through stable PN without taking any other measures. The primary pathways for nitrogen removal were identified as denitrification, simultaneous nitrification-denitrification, and aerobic denitrification. High-throughput sequencing analysis revealed that the immobilized fillers facilitated the autonomous enrichment of functional bacteria in each reactor, effectively promoting the dominance and stability of the microbial communities. In addition, GI-PN/D had the characteristic of low sludge yield, with an average sludge yield of 0.029 kg SS/kg COD. This study provides an effective technical for nitrogen removal from municipal wastewater through PN. [ABSTRACT FROM AUTHOR]

Recent advancements in RNA three-dimensional (3D) structure prediction have provided significant insights into RNA biology, highlighting the essential role of RNA in cellular functions and its therapeutic potential. This review summarizes the latest developments in computational methods, particularly the incorporation of artificial intelligence and machine learning, which have improved the efficiency and accuracy of RNA structure predictions. We also discuss the integration of new experimental data types, including cryoelectron microscopy (cryo-EM) techniques and high-throughput sequencing, which have transformed RNA structure modeling. The combination of experimental advances with computational methods represents a significant leap in RNA structure determination. We review the outcomes of RNA-Puzzles and critical assessment of structure prediction (CASP) challenges, which assess the state of the field and limitations of existing methods. Future perspectives are discussed, focusing on the impact of RNA 3D structure prediction on understanding RNA mechanisms and its implications for drug discovery and RNA-targeted therapies, opening new avenues in molecular biology. In this review, Mukherjee et al. discuss the latest computational methods for RNA 3D structure prediction in light of outcomes from the RNA-Puzzles and CASP prediction challenges. They cover advances in simulation-based methods, recent deep learning techniques, and methods incorporating experimental data, and outline potential future developments. [ABSTRACT FROM AUTHOR]

• APC and TP53 mutations are the most common genetic variants found in Persian patients. • KRAS and ERBB2 variants are associated with specific tumor sites. • These findings provide a basis for personalized treatment strategies in CRC. Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality, and understanding the genetic landscape is crucial for improving targeted therapies. This study aimed to analyze the tumor's genetic profiles of patients with metastatic CRC, focusing on pathogenic or likely pathogenic variants in tumor related genes. The present cross-sectional study was conducted on 40 Persian patients with metastatic colorectal adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples were analyzed using next generation sequencing technique to detect pathogenic variants. The patients' tumor characteristics, including differentiation grades and tumor sites (colon, rectum, or rectosigmoid), were documented and the relationship between variants and tumor characteristics was evaluated. The study population had a mean age of 55.75 ± 12.88 years, and 60 % were female. The most common tumor site was the colon (52.5 %), followed by rectosigmoid (27.5 %) and cecum (20 %). APC gene variants were prevalent in 72.5 % of patients, with the p.Arg876* variant being the most frequent. TP53 gene variants were present in 65 %, with p.Trp146* and p.Arg273His being the most common. Pathogenic KRAS gene variants were observed in 50 %, significantly associated with rectosigmoid involvement (p = 0.001). The ERBB2 CNVs were found in 25 % of patients and were associated with colon involvement (p = 0.021). The study highlights the genetic diversity in Persian patients with metastatic colon adenocarcinoma and demonstrated that APC and TP53 variants were the most prevalent, while KRAS and ERBB2 variants were associated with specific tumor sites. These findings provide a basis for personalized treatment strategies in CRC among Persian population. [ABSTRACT FROM AUTHOR]

• We identified gene mutations that can potentially influence disease characteristics and prognosis in newly diagnosed multiple myeloma. • Among genes associated with disease characteristics, we identified alterations of single genes (PIK3C2B, ARID1B) or combinations of genes (KMT2B, FAT1, and ARID1B) differently influencing progression-free survival. • The results support prognostic stratification and multiple genes influencing progression-free survival belong to the druggable and clinically actionable gene categories, which may lead to improved clinical management and treatment strategies in the future. The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes. A total of 724 high-quality variants were validated. All patients harbored mutations associated with the RTK-RAS pathway, with over half having alterations in PI3 K, NOTCH, and WNT pathways. Several gene mutations were associated with specific clinical characteristics and prognostic indicators, revealing a complex interplay between genetic alterations and myeloma type, standard prognostic indicators, biochemical parameters, and renal function. Genetic alterations significantly influencing progression-free survival concerned PIK3C2B, ARID1B genes, and concomitant mutations in KMT2B, FAT1 , and ARID1B. The findings underscore the potential of gene mutation-based prognostic tools in enhancing clinical decision-making and suggest that further exploration of identified genetic markers could pave the way for improved prognostic stratification and targeted therapeutic interventions in multiple myeloma. [ABSTRACT FROM AUTHOR]

Daqu, a crucial fermentation starter in the production of various Chinese fermented foods, plays a pivotal role in shaping complex enzyme profiles and diverse flavour precursors. This review aims to elucidate the microbial communities within Daqu, focusing on their functionalities in the context of flavour development. We delve into the detection methods of microorganisms and flavour substances in Daqu, employing advanced technologies including high-performance liquid chromatography, gas chromatography, pseudo-targeted metabolomics, and headspace solid-phase microextraction-gas chromatography-mass spectrometry. This review explores high throughput sequencing technologies, including pyrosequencing, clonal library sequencing, metaproteomic, and metagenomics, to gain a comprehensive understanding of the intricate microbial dynamics. Additionally, we discuss the metabolic pathways involved in flavour substance production within Daqu. By synthesizing information on Daqu types, microorganisms present, detection methodologies, and flavour substance metabolic pathways, this review contributes to a deeper comprehension of the intricate processes underpinning the Flavors of Chinese fermented foods. [Display omitted] • Crucial role of Daqu in enzyme profiles and flavor precursors in Chinese foods. • Microbial communities in Daqu and their role in flavor development. • High throughput sequencing: pyrosequencing, clonal library sequencing, metaproteomic, metagenomics. • Comprehensive synthesis of Daqu types, microorganisms, and metabolic pathways. [ABSTRACT FROM AUTHOR]

Silica particles can cause silicosis, a disease characterized by diffuse fibrosis of the lungs. Various signaling pathways composed of different types of cells and cytokines are involved in the development of silicosis. Exosomes have become a research hotspot recently. However, the role of exosomal microRNA (miRNA) in silicosis remains unclear. In this study, we generated exosomal miRNA sequences from exosomes isolated from bronchoalveolar lavage fluid (BALF) of silicosis patients and the control group by high-throughput sequencing. Functional annotation and analysis of miRNA identified key target miRNAs. Levels of target miRNAs were analyzed in patient and animal samples and cells. Effects of increased miRNA were assessed through protein levels in target signaling pathways in cells treated with silica, miRNA mimics, and inhibitors. Our study identified 40 up-regulated and 70 down-regulated miRNAs, with miR-552–3p and its putative target gene Caveolin 1 (CAV1) as targets for further research. We found that the levels of exosomal miR-552–3p increased in silicosis patients' BALF samples, silicosis model mice, and A549 cells exposed to silica. Inhibition of miR-552–3p suppressed the expression of fibrosis markers. The increased miR-552–3p leads to the up-regulation of fibronectin and α-smooth muscle actin (α-SMA) and the suppression of caveolin 1 in fibroblast cells. Mitogen-activated protein kinase (MAPK) signaling pathways are activated in cells treated with silica and miR-552–3p mimics. These results help to understand exosomal miRNA-mediated intercellular communication and its key role in fibroblast activation and silicosis. [Display omitted] • This study identifies exosome-induced fibroblast proliferation in silicosis BALF. • The pro-fibrosis impact of epithelial cell-derived exosomes on fibroblasts is documented. • Observations show elevated miR-552-3p expression in silica-exposed A549, HPAEpiC cells, and their exosomes. • Study associates miR-552-3p upregulation with silicosis, confirms CAV 1 binding. • Exosome transport of epithelial miR-552-3p to fibroblasts results in phenotype transdifferentiation. [ABSTRACT FROM AUTHOR]

Genomic tumour profiling has a crucial role in the management of patients with solid cancers, as it helps selecting and prioritising therapeutic interventions based on prognostic and predictive biomarkers, as well as identifying markers of hereditary cancers. Harmonised approaches to interpret the results of genomic testing are needed to support physicians in their decision making, prevent inequalities in precision medicine and maximise patient benefit from available cancer management options. The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group assembled a group of international experts to propose recommendations for preparing clinical genomic reports for solid cancers. These recommendations aim to foster best practices in integrating genomic testing within clinical settings. After review of available evidence, several rounds of surveys and focused discussions were conducted to reach consensus on the recommendation statements. Only consensus recommendations were reported. Recommendation statements were graded in two tiers based on their clinical importance: level A (required to maintain common standards in reporting) and level B (optional but necessary to achieve ideal practice). Genomics reports should present key information in a front page(s) followed by supplementary information in one or more appendices. Reports should be structured into sections: (i) patient and sample details; (ii) assay and data analysis characteristics; (iii) sample-specific assay performance and quality control; (iv) genomic alterations and their functional annotation; (v) clinical actionability assessment and matching to potential therapy indications; and (vi) summary of the main findings. Specific recommendations to prepare each of these sections are made. We present a set of recommendations aimed at structuring genomics reports to enhance physician comprehension of genomic profiling results for solid cancers. Communication between ordering physicians and professionals reporting genomic data is key to minimise uncertainties and to optimise the impact of genomic tests in patient care. • These Recommendations cover the preparation of genomic reports to inform clinical decisions for patients with solid cancers. • Recommendations are based on consensus from a multidisciplinary group of experts after reviewing available evidence. • The manuscript provides guidance on structuring genomic reports, and the optimal presentation of content for each section. • These recommendations are relevant to most next-generation sequencing assays utilised in clinical practice and research. • Recommendations are categorised into priority levels (A, B) to adapt to diverse clinical and laboratory contexts. [ABSTRACT FROM AUTHOR]

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification. [ABSTRACT FROM AUTHOR]

Cortisol is a glucocorticoid hormone that has immunosuppressive function. Elevated basal cortisol levels are present in patients with some kinds of cancers, but its role in the microenvironment of pancreatic adenocarcinoma (PAAD) remains unclear. This study analyzed the expression of genes involved in cortisol generation by using high-throughput sequencing data from TCGA portal and found HSD11B1 was significantly upregulated in patients with PAAD. The correlations between HSD11B1 level and the expression of 23 immunosuppressive receptors were analyzed by Spearman's correlation analysis. The function of HSD11B1 was examined in primary NK cells and PAAD cell lines. The levels of cortisol in medium and cell lysates were detected by ELISA. In vitro killing assay was used to evaluate the cytotoxicity of NK cells. Cell surface levels of CD96, Tim-3, PD-1, TIGIT, CTLA-4, NKp46, NKp30, NKD2G and LFA-1A, and intracellular levels of CD107a and IFN-γ were examined by flow cytometry. We observed that patients with higher HSD11B1 level had shorter survival time. HSD11B1 is positively correlated with the mRNA levels of 11 immunosuppressive receptors in PAAD. Higher HSD11B1 level relates to reduced abundance of activated NK cells in the tumors. HSD11B1 overexpressed NK cells exhibit exhausted phenotype with increased cortisol production, reduced viability, and reduced cytotoxicity against cancer cells. Overexpression of HSD11B1 did not change the viability of tumor cells but upregulated cortisol production. Targeting HSD11B1 by a specific inhibitor improved the NK cells responsiveness. In conclusion, HSD11B1 is upregulated in patients with PAAD, and higher HSD11B1 level is related to poor prognosis. Upregulation of HSD11B1 in NK and tumor cells increased the production and secretion of cortisol and induces NK cell exhaustion. • HSD11B1 is overexpressed in pancreatic cancer which relates to raised cortisol level. • Higher HSD11B1 level relates to reduced activated NK cells number in the tumor. • Overexpression of HSD11B1 in NK cells induces exhausted phenotypes. • Overexpression of HSD11B1 in tumor cells upregulates cortisol production. • Targeting HSD11B1 in tumor cells improve the NK cells responsiveness. [ABSTRACT FROM AUTHOR]

• In Beijing's super sandstorm 2021, 5700 amplicon sequence variants were detected. • Airborne bacteria in sandstorms were compared with the after-storm and haze days. • The sandstorm newly brought 10 pathogenic bacterial genera to the atmosphere. • Small bioaerosols (0.65–1.1 µm) were still suspended after the sandstorm subsided. Sandstorm, which injects generous newly emerging microbes into the atmosphere covering cities, adversely affects the air quality in built environments. However, few studies have examined the change of airborne bacteria during severe sandstorm events. In this work, we analyzed the airborne bacteria during one of the strongest sandstorms in East Asia on March 15th, 2021, which affected large areas of China and Mongolia. The characteristics of the sandstorm were compared with those of the subsequent clean and haze days. The composition of the bacterial community of air samples was investigated using quantitative polymerase chain reaction (qPCR) and high-throughput sequencing technology. During the sandstorm, the particulate matter (PM) concentration and bacterial richness were extremely high (PM 2.5 : 207 µg/m3; PM 10 : 1630 µg/m3; 5700 amplicon sequence variants/m3). In addition, the sandstorm brought 10 pathogenic bacterial genera to the atmosphere, posing a grave hazard to human health. As the sandstorm subsided, small bioaerosols (0.65–1.1 µm) with a similar bacterial community remained suspended in the atmosphere, bringing possible long-lasting health risks. [Display omitted] [ABSTRACT FROM AUTHOR]

Within neurosurgery, it has always been important to individualize patient care. In recent years, however, technological advances have brought a new dimension to personalized care as developing methods, including next-generation sequencing, have enabled us to molecularly profile pathologies with increasing scale and resolution. In this review, the authors discuss the history and advances in precision medicine and neurosurgery, focusing both on neuro-oncology, as well as its extension to other neurosurgical subspecialties. They highlight the important roles of neurosurgeons in past work and future work, with the extension of tissue collection and precision medicine principles to additional sample types and disease indications. [ABSTRACT FROM AUTHOR]

Recent developments in technology have led to rapid advances in precision medicine, especially due to the rise of next-generation sequencing and molecular profiling. These technological advances have led to rapid advances in research, including increased tumor subtype resolution, new therapeutic agents, and mechanistic insights. Certain therapies have even been approved for molecular biomarkers across histopathological diagnoses; however, translation of research findings to the clinic still faces a number of challenges. In this review, the authors discuss several key challenges to the clinical integration of precision medicine, including the blood-brain barrier, both a lack and excess of molecular targets, and tumor heterogeneity/escape from therapy. They also highlight a few key efforts to address these challenges, including new frontiers in drug delivery, a rapidly expanding treatment repertoire, and improvements in active response monitoring. With continued improvements and developments, the authors anticipate that precision medicine will increasingly become the gold standard for clinical care. [ABSTRACT FROM AUTHOR]

The past two decades have witnessed a rapid increase in the genomic sequencing of parasitoid wasps, amassing a rich dataset for detailed studies. Genome size variability in parasitoid wasps is linked to the dynamic evolution of transposable elements. Genomic studies have discovered that a number of genomic changes may be linked to key traits in parasitoid wasps, such as reduced body size, host range shift, and sex determination. The genomic data provide robust support for studying the diversity and evolution of parasitic effectors, including venoms and polydnaviruses. Deeper genomic research is poised to provide insights into the evolution of parasitoid diversity, and the genomic knowledge obtained could be used for enhancing the application of parasitoid wasps in biological control. Parasitoid wasps represent a group of parasitic insects with high species diversity that have played a pivotal role in biological control and evolutionary studies. Over the past 20 years, developments in genomics have greatly enhanced our understanding of the biology of these species. Technological leaps in sequencing have facilitated the improvement of genome quality and quantity, leading to the availability of hundreds of parasitoid wasp genomes. Here, we summarize recent progress in parasitoid wasp genomics, focusing on the evolution of genome size (GS) and the genomic basis of several key traits. We also discuss the contributions of genomics in studying venom evolution and endogenization of viruses. Finally, we advocate for increased sequencing and functional research to better understand parasitoid biology and enhance biological control. [ABSTRACT FROM AUTHOR]

Primary liver tumours, including benign liver tumours, hepatocellular carcinoma and cholangiocarcinoma, present a multifaceted challenge, necessitating a collaborative approach, as evidenced by the role of the multidisciplinary tumour board (MDTB). The approach to managing primary liver tumours involves specialised teams, including surgeons, radiologists, oncologists, pathologists, hepatologists, and radiation oncologists, coming together to propose individualised treatment plans. The evolving landscape of primary liver cancer treatment introduces complexities, particularly with the expanding array of systemic and locoregional therapies, alongside the potential integration of molecular biology and artificial intelligence (AI) into MDTBs in the future. Precision medicine demands collaboration across disciplines, challenging traditional frameworks. In the next decade, we anticipate the convergence of AI, molecular biology, pathology, and advanced imaging, requiring adaptability in MDTB structure to incorporate these cutting-edge technologies. Navigating this evolution also requires a focus on enhancing basic, translational, and clinical research, as well as boosting clinical trials through an upgraded use of MDTBs as hubs for scientific collaboration and raising literacy about AI and new technologies. In this review, we will delineate the current unmet needs in the clinical management of primary liver cancers, discuss our perspective on the future role of MDTBs in primary liver cancers ("next generation" MDTBs), and unravel the potential power and limitations of novel technologies that may shape the multidisciplinary care landscape for primary liver cancers in the coming decade. [ABSTRACT FROM AUTHOR]

Bilateral communication between bones and muscles is essential for healing composite bone–muscle injuries from orthopedic surgeries and trauma. However, these injuries are often characterized by exaggerated inflammation, which can disrupt bone–muscle crosstalk, thereby seriously delaying the healing of either tissue. Existing approaches are largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging, with little research conducted to date. Here we introduce collagen patches that overcome this overlooked issue by harnessing the plasticity of macrophage phenotypes. Phosphatidylserine liposomes (PSLs) capable of shifting the macrophage phenotype from inflammatory M1 into anti-inflammatory/prohealing M2 were coated on collagen patches via a layer-by-layer method. Original collagen patches failed to improve tissue healing under inflammatory conditions coordinated by M1 macrophages. In contrast, PSL-coated collagen patches succeeded in accelerating bone and muscle healing by inducing a microenvironment dominated by M2 macrophages. In cell experiments, differentiation of preosteoblasts and myoblasts was completely inhibited by secretions of M1 macrophages but unaffected by those of M2 macrophages. RNA-seq analysis revealed that type I interferon and interleukin-6 signaling pathways were commonly upregulated in preosteoblasts and myoblasts upon stimulation with M1 macrophage secretions, thereby compromising their differentiation. This study demonstrates the benefit of PSL-mediated M1-to-M2 macrophage polarization for simultaneous bone and muscle healing, offering a potential strategy toward simultaneous regeneration of multiple tissues. Existing approaches for tissue regeneration, which primarily utilize growth factors, have been largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging and has been little studied. Here we demonstrate that collagen patches releasing phosphatidylserine liposomes (PSLs) promote M1-to-M2 macrophage polarization and are effective for simultaneous healing of bone and muscle. Transcriptome analysis using next-generation sequencing reveals that differentiation of preosteoblasts and myoblasts is inhibited by the secretions of M1 macrophages but promoted by those of M2 macrophages, highlighting the importance of timely regulation of M1-to-M2 polarization in tissue regeneration. These findings provide new insight to tissue healing of multiple tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

Eukaryotic plankton play an important role in the wetland lake ecosystems. However, the size structure and species composition of eukaryotic plankton in shallow wetland lake ecosystems remains largely unexplored. To address this gap, our study employed high-throughput sequencing and quantitative PCR techniques to investigate the size structure (pico-0.7–5 μm and nano-5–20 μm) and species composition of eukaryotic plankton in two shallow wetland lakes in China during August 2016. Our findings reveal that the diversity index values of the pico-size fraction were significantly higher than those of the nano-size fraction. Additionally, there was a significant difference in community structure between these two size fractions. Furthermore, different dominant taxa were associated with each particle size, with certain lineages being enriched exclusively in one of the size fractions. In particular, biomarkers differed between the pico- and nano- fractions. The abundance of the 18S rDNA gene did not differ significantly between the two fractions. However, there was a significant difference in the abundance of gene transcripts. Moreover, the pico- fraction exhibited a significantly higher rRNA: rDNA ratio compared to the nano- fraction. It is important to note that certain taxa had lower absolute abundance in specific samples, despite their higher relative abundance. [ABSTRACT FROM AUTHOR]

Anthropogenic perturbations make negative effects on wetland ecosystems, such as increasing levels of eutrophication. Under variable environmental conditions, studying the processes and mechanisms underlying their spatial distribution is critical to biogeochemical significance of microorganisms. In order to understand the changes in sediment bacterial community and their assembly with long-term eutrophication of the Baiyangdian Lake of China, we explored the microbial communities for 24 surface sediment samples using high throughput sequencing of V3-V4 region of 16S rRNA gene, meanwhile we employed Neutral community model (NCM) to characterize the community assembly processes. Then, the β-nearest taxon index (βNTI) based on a null model was used to provide a quantitative description of the assembly processes of the bacterial community. Dispersal limitation, quantified by βNTI, accounted for ∼64.6% of all assembly processes. As the increasing levels of eutrophication, deterministic processes of bacterial community assembly may be enhanced. Moreover, the significant correlation between the βNTI and change in water NO 3 − or sediment pH might lead to deterministic processes. There was some selection pressure acting within the Baiyangdian lake sediments. The neutral community model properly explained bacterial community assembly. The NO 3 −, NH 4 +, pH and EC were main influencing factors on the composition of the bacterial community. The overlying water NO 3 −, surface water NO 3 − and sediment pH were the three most crucial environmental factors to drive bacterial assembly. The findings revealed that Group 4 with relatively stronger deterministic processes as a more eutrophic area should be monitored as an indicator for eutrophication governance. [ABSTRACT FROM AUTHOR]

• Number of cells collected or irradiation cycles do not affect mosaicism percent. • Incidence of mosaicism increases with repeated freeze–thaw cycles. • However, the embryos remain suitable for transfer. • Detection of mosaicism in NGS might affect the results. • PGT-A can be performed using frozen embryos. In preimplantation genetic testing for aneuploidy, opinions regarding the handling of mosaic embryos vary. In this study, we aimed to investigate the effects of freeze-thawing, the number of cells obtained, and the number of laser irradiation cycles on the degree of embryonic mosaicism. This study was conducted in three parts. First, we classified specimens into the normal biopsy (control) (119 patients, 304 blastocysts) and thawed-biopsy (TB group) (26 patients, 72 blastocysts)) groups. The control and TB groups were then classified into three categories (euploidy, mosaic and aneuploidy) according to next-generation sequencing (NGS) results, and the number of cells collected and laser irradiation cycles were compared for each category. Subsequently, the effects of differences in the number of cells collected and laser irradiation cycles on NGS results were investigated in the control and TB groups. Finally, data on cell collection and laser irradiation cycles and NGS analysis results for the groups were compared. The TB group had a significantly higher incidence of chromosomal mosaicism than the control group. Neither the number of cells collected nor the laser irradiation cycles affected the percentage of chromosomal mosaicism. However, the freeze–thaw process increased the occurrence of mosaicism. This study showed that repeated freeze–thaw cycles increase the incidence of mosaicism, but the embryos are not aneuploid and are therefore suitable for transfer. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a global public health threat, and the development of rapid and precise diagnostic tools is the key to enabling the early start of treatment, monitoring response to treatment, and preventing the spread of the disease. An overview of recent progress in host- and pathogen-based TB diagnostics. We conducted a PubMed search of recent relevant articles and guidelines on TB screening and diagnosis. An overview of currently used methods and perspectives in the following areas of TB diagnostics is provided: immune-based diagnostics, X-ray, clinical symptoms and scores, cough detection, culture of Mycobacterium tuberculosis and identifying its resistance profile using phenotypic and genotypic methods, including next-generation sequencing, sputum- and non–sputum-based molecular diagnosis of TB and monitoring of response to treatment. A brief overview of the most relevant advances and changes in international guidelines regarding screening and diagnosing TB is provided in this review. It aims at reviewing all relevant areas of diagnostics, including both pathogen- and host-based methods. [ABSTRACT FROM AUTHOR]

The commonly used isomiR format (mirGFF3) combined with classification guidelines has been proposed to facilitate communication within the field. New technological and computational advances have validated certain isomiRs as biologically relevant. Various experimental studies have shown mediation of different regulation mechanisms through isomiRs as opposed to regulation mediated via archetypal miRNAs. In cancer, isomiRs have been identified as promising biomarkers in solid tissue for prognosis, and in circulatory fluids for diagnosis. Additionally, an isomiR has been identified as a promising therapeutic target. Similar studies are under way in the context of neurodegenerative, cardiovascular, and metabolic diseases. MicroRNAs (miRNAs) and isoforms of their archetype, called isomiRs, regulate gene expression via complementary base-pair binding to messenger RNAs (mRNAs). The partially evolutionarily conserved isomiR sequence variations are differentially expressed among tissues, populations, and genders, and between healthy and diseased states. Aiming towards the clinical use of isomiRs as diagnostic biomarkers and for therapeutic purposes, several challenges need to be addressed, including (i) clarification of isomiR definition, (ii) improved annotation in databases with new standardization (such as the mirGFF3 format), and (iii) improved methods of isomiR detection, functional verification, and in silico analysis. In this review we discuss the respective challenges, and highlight the opportunities for clinical use of isomiRs, especially in the light of increasing amounts of next-generation sequencing (NGS) data. [ABSTRACT FROM AUTHOR]

A key hurdle in broader next-generation sequencing (NGS) biomarker testing access in oncology is the ongoing debate on NGS's cost-effectiveness. We conducted a systematic review of existing evidence of the costs of NGS as a biomarker testing strategy in oncology and developed policy suggestions. We searched multiple databases for studies reporting cost comparisons and cost-effectiveness of NGS across oncology indications and geographies between 2017 and 2022, inclusive. Inclusion criteria were established based on indication and type of cost-effectiveness analysis provided. We validated analyses and policy recommendations with 5 payer/policy maker interviews in the United States, Europe, and United Kingdom. Of the 634 identified studies, 29 met inclusion criteria, spanning 12 countries and 6 indications. Cost comparisons of NGS were evaluated using 3 methodologies: (1) comparison of direct testing costs, (2) comparison of holistic testing costs, and (3) comparison of long-term patient outcomes and costs. Targeted panel testing (2-52 genes) was considered cost-effective when 4+ genes were assessed, and larger panels (hundreds of genes) were generally not cost-effective. Holistic analysis demonstrated that NGS reduces turnaround time, healthcare staff requirements, number of hospital visits, and hospital costs. Finally, studies evaluating NGS testing including the cost of targeted therapies generally found the incremental cost-effectiveness ratio to be above common thresholds but highlighted valuable patient benefits. Current literature supports NGS's cost-effectiveness as an oncology biomarker testing strategy under specific conditions. These findings underscore the need to develop policies to support holistic assessment of NGS to ensure appropriate reimbursement and access. • Currently, biomarker testing in oncology largely relies on single-gene biomarker assays, which are inexpensive and readily accessible, but only detect a single mutation. The adoption of next-generation sequencing (NGS), a technology that enables simultaneous detection of multiple biomarkers, can provide considerable clinical advantages but questions on its cost-effectiveness hinder wider adoption. • Our research shows that targeted panel testing, a form of NGS, reduces costs compared with conventional single-gene biomarker assays across several oncology indications and geographies when 4+ genes require testing. Moreover, when holistic testing costs (eg, turnaround time, healthcare personnel costs, number of hospital visits) are considered in the analysis, targeted panel testing consistently provides cost savings versus single-gene testing. • To fully realize the economic and societal benefits of NGS biomarker testing, cost comparisons or cost-effectiveness analyses should consider holistic testing costs. Moreover, comparative cost or cost-effectiveness should not hinder the reimbursement of NGS as a biomarker testing strategy in specific situations today. Measures must be implemented to broaden access, reimbursement, and testing infrastructure as the relative cost of NGS decreases. [ABSTRACT FROM AUTHOR]

Summary: Next Generation Sequencing (NGS) technologies offer affordable ways to study craniofacial growth and development patterns in orthodontic patients, including patients with rare congenital disorders, to learn more about the gene regulatory networks that govern various aspects of craniofacial complex [Display omitted] With the development of Sanger DNA Sequencing in the 1970's, the scientific community gained a new tool to understand relationships between phenotype and genotype. This methodology allowed one to sequence small regions of DNA in the human genome, but was expensive, time consuming and used radioactive labels; making it impractical to use to study an entire human genome. As technologies improved, DNA amplification by polymerase chain reaction (PCR) in the 1980's allowed scientists to selectively amplify a targeted DNA sequence. This advancement, along with the utilization of fluorescently–labeled nucleotides significantly influenced the automation of sequencing technology. Today, Next–Generation Sequencing (NGS) can affordably sequence millions of DNA fragments simultaneously and is being used to examine the entire code of the human genome. This capability is revolutionary and offers new hope in identifying key genes involved in numerous craniofacial anomalies. [ABSTRACT FROM AUTHOR]

Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo , one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. The diagnostic yield of WES was 48.8 %. We conclude that patients' characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype. [ABSTRACT FROM AUTHOR]

To evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era. The study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing). The diagnostic utility of genetic testing was evaluated to compare the early-NGS period (2005 to 2013, n = 183) and the NGS era (2014 to 2021, n = 131). An ESD was established in 221 of 314 (70.4%) infants with IESS: structural, 40.8%; genetic, 17.2%; metabolic, 8.3%; immune-infectious, 4.1%. The diagnostic yield of genetic testing increased from 8.9% to 41.7% in the cohort during the four follow-up periods. The rate of unknown etiology decreased from 34.9% to 22.1% during the follow-up periods. The genetic ESD was established as 27.4% with genetic testing in the NGS era. The genetic testing in the NGS era increased dramatically in subgroups with unknown and structural etiologies. The diagnostic yields of the epilepsy panels increased from 7.6% to 19.2%. However, the diagnostic yield of whole exome sequencing remained at similar levels during the early-NGS period at 54.5% and in the NGS era at 59%. The more genetic ESD (27.4%) was defined for IESS in the NGS era with the implication of precision therapy (37.7%). [ABSTRACT FROM AUTHOR]

With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications. Developmental and epileptic encephalopathies, the coexistence of neurodevelopmental comorbidities, early age of epilepsy onset, unexplained drug-refractory epilepsy, and positive family history have demonstrated the highest likelihood of yielding positive genetic test results. Given the diagnostic efficacy across different testing modalities, reducing costs of next-generation sequencing tests, and genetic diversity of epilepsies, exome sequencing or genome sequencing, where feasible and available, have been recommended as the first-tier test. Comprehensive clinical phenotyping at the outset, corroborative evidence from radiology and electrophysiology-based investigations, reverse phenotyping, and periodic reanalysis are some of the valuable strategies when faced with inconclusive test results. In this narrative review, the authors aim to simplify the approach to genetic testing in epilepsy by guiding on the selection of appropriate testing tools in the indicated clinical scenarios, addressing crucial aspects during pre- and post-test counseling sessions, adeptly navigating the traps posed by uncertain or negative genetic variants, and paving the way forward to the emerging testing modalities beyond DNA sequencing. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs. To investigate the role of senescent CD4+ T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis. We explored the expression levels of p16INK4a and p21, classical markers of cellular senescence, in CD4+ T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis. Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16INK4a and p21 in CD4+ T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor (TCR) α and β chains, and expression of Tet methylcytosine dioxygenase 2 (Tet2) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4creTet2f/f mice was milder than that in Tet2f/f mice in the IMQ-induced psoriasis model. We revealed the roles of senescent CD4+ T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αβ repertoire, and regulation of the TET2-Th17 cell pathway. • We highlight the crucial role of senescent CD4+ T cells in pathogenesis of psoriasis. • The TET2 emerges as an important regulator of senescent CD4+ T cells in psoriasis. • Topical ABT-737 gel shows potential as a therapy for psoriasis by eliminating senescent cells. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common condition associated with significant morbidity, mortality, and cost. Injured kidney tissue can regenerate after many forms of AKI. However, there are no treatments in routine clinical practice to encourage recovery. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that orchestrate kidney recovery. The advent of high-throughput sequencing technologies and genetic mouse models has opened an unprecedented window into the transcriptional dynamics that accompany both successful and maladaptive repair. AKI recovery shares similar cell-state transformations with kidney development, which can suggest common mechanisms of gene regulation. Several powerful bioinformatic strategies have been developed to infer the activity of gene regulatory networks by combining multiple forms of sequencing data at single-cell resolution. These studies highlight not only shared stress responses but also key changes in gene regulatory networks controlling metabolism. Furthermore, chromatin immunoprecipitation studies in injured kidneys have revealed dynamic epigenetic modifications at enhancer elements near target genes. This review will highlight how these studies have enhanced our understanding of gene regulation in injury response and regeneration. [ABSTRACT FROM AUTHOR]

Next-generation sequencing technologies have significantly increased the availability of genomic databases. These databases can be used for numerous applications in genome-wide association studies, such as disease prediction and precision medicine. Missing values in genotype data diminish the database quality. Genotype imputation is an essential low-cost tool in genomics that statistically infers missing genotype variants from an experimentally observed set of variants. Owing to the computationally intensive nature of the problem, genotype imputation is often outsourced to an external service provider. However, sharing genomic data as a plaintext raises privacy concerns and leaks sensitive information. Existing privacy-preserving approaches perform genotype imputation using linear classification models, which require training a separate classifier for each variant using previously labeled data. Self-supervised deep learning models, such as autoencoders, have recently become popular because of their ability to model complex patterns in genomic datasets and achieve significantly high accuracy. However, deep learning-based genotype imputation under a privacy-preserving setting remains largely unexplored. In this work, we propose a novel adaptation of an autoencoder-based genotype imputation model that preserves the privacy of sensitive genomic data. To our knowledge, ours is the first work to do so. Genomic data privacy is preserved using fully homomorphic encryption (FHE). FHE schemes enable Efficient computations over encrypted data but suffer from noise growth as the number of computations increases. To overcome the issue of noise growth due to computationally complex deep learning, we use neural network quantization, which considerably reduces the network size while achieving high accuracy, as demonstrated in our results. We present all the necessary parameters to perform deep learning-based genotype imputation in the privacy-preserving setting. [ABSTRACT FROM AUTHOR]

Next-Generation Sequencing has revolutionized the study of genetic mutations, enabling large-scale investigations into their roles in disease development. However, extracting meaningful insights from the vast amount of biomedical literature remains a complex challenge that cannot be addressed manually. In this paper, we present pre-trained models (PTMs) for the automatic extraction of relations from biomedical text, specifically targeting the variant-phenotype domain. Our evaluation on the SNPPhenA corpus demonstrates that fine-tuning small BERT-based models, particularly DeBERTa, yields strong performance, approaching the current state-of-the-art (SOTA). Additionally, our results indicate that carefully fine-tuning Google's Gemini Pro 1.0 outperforms the existing SOTA for both sentence-level tasks (where the model processes only the target sentence) and abstract-level tasks (where the model processes the entire abstract). [ABSTRACT FROM AUTHOR]

• Clinical sensitivity of whole-gene sequencing is higher than standard genetic tests. • One CFTR variant and sweat [Cl-] ≥60 mEq/L predicts the presence of a 2nd variant. • Negative conventional CFTR genetic tests should prompt clinical phenotype review. Cystic fibrosis (CF) is caused by deleterious variants in each CFTR gene. We investigated the utility of whole-gene CFTR sequencing when fewer than two pathogenic or likely pathogenic (P/LP) variants were detected by conventional testing (sequencing of exons and flanking introns) of CFTR. Individuals with features of CF and a CF-diagnostic sweat chloride concentration with zero or one P/LP variants identified by conventional testing enrolled in the CF Mutation Analysis Program (MAP) underwent whole-gene CFTR sequencing. Replication was performed on individuals enrolled in the CF Genome Project (CFGP), followed by phenotype review and interrogation of other genes. Whole-gene sequencing identified a second P/LP variant in 20/43 MAP enrollees (47 %) and 10/22 CFGP enrollees (45 %) who had one P/LP variant after conventional testing. No P/LP variants were detected when conventional testing was negative (MAP: n = 43; CFGP: n = 13). Genome-wide analysis was unable to find an alternative etiology in CFGP participants with fewer than two P/LP CFTR variants and CF could not be confirmed in 91 % following phenotype re-review. Whole-gene CFTR analysis is beneficial in individuals with one previously-identified P/LP variant and a CF-diagnostic sweat chloride. Negative conventional CFTR testing indicates that the phenotype should be re-evaluated. [ABSTRACT FROM AUTHOR]

Allopolyploids are individuals that have two or more complete sets of chromosomes derived from different species. The number of chromosome-scaled allopolyploid genomes assembled has increased as genome sequencing has become cheaper, longer, and more accurate. Several computational tools have been developed to leverage differences in biology between progenitor species to identify subgenomes of allopolyploids. Whole-genome duplications (WGDs) are widespread genomic events in eukaryotes that are hypothesized to contribute to the evolutionary success of many lineages, including flowering plants, Saccharomyces yeast, and vertebrates. WGDs generally can be classified into autopolyploids (ploidy increase descended from one species) or allopolyploids (ploidy increase descended from multiple species). Assignment of allopolyploid progenitor species (called subgenomes in the polyploid) is important to understanding the biology and evolution of polyploids, including the asymmetric subgenome evolution following hybridization (biased fractionation). Here, I review the different methodologies used to identify the ancestors of allopolyploid subgenomes, discuss the advantages and disadvantages of these methods, and outline the implications of how these methods affect the subsequent evolutionary analysis of these genomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Risk factors shaping host-parasite interactions impact the clinical management of canine leishmaniosis. • Renal and ocular findings are major risk factors for LeishVet stages III and IV. • Diagnosis of comorbidities is key to managing dogs with leishmaniosis, although independent of their clinical outcome. • A complex polygenic component underlies the development of severe clinical forms of leishmaniosis in certain purebred dogs. • Protective immunity against Leishmania parasites is related to genetic factors involved in the ER stress and UPR pathways. Canine leishmaniosis (CanL), caused by Leishmania infantum , is a complex disease of growing importance in Europe. Clinical manifestations result from the down-modulation of the host immune response through multiple host-parasite interactions. Although several factors might influence CanL progression, this is the first known study evaluating risk factors for its different clinical stages in a large referral hospital population (n = 35.669) from an endemic area, over a 20 year period. Genome-wide scans for selection signatures were also conducted to explore the genomic component of clinical susceptibility to L. infantum infection. The prevalence of CanL was 3.2% (16.7% stage I; 43.6% stage II; 32.1% stage III; 7.6% stage IV). Dog breed (crossbreed), bodyweight (<10 kg), living conditions (indoors), regular deworming treatment, and being vaccinated against Leishmania significantly decreased the transmission risk and the risk for developing severe clinical forms. Conversely, the detection of comorbidities was associated with advanced clinical forms, particularly chronic kidney disease, neoplasia, cryptorchidism, infectious tracheobronchitis and urate urolithiasis, although those did not impact the clinical outcome. Significant associations between an increased risk of severe clinical stages and findings in the anamnesis (renal or skin-related manifestations) and physical examination (ocular findings) were also detected, highlighting their diagnostic value in referred cases of CanL. Sixteen breeds were found to be significantly more susceptible to developing severe stages of leishmaniosis (e.g. Great Dane, Rottweiler, English Springer Spaniel, Boxer, American Staffordshire Terrier, Golden Retriever), while 20 breeds displayed a clinical resistantance phenotype and, thus, are more likely to mount an efficient immune response against L. infantum (e.g. Pointer, Samoyed, Spanish Mastiff, Spanish Greyhound, English Setter, Siberian Husky). Genomic analyses of these breeds retrieved 12 regions under selection, 63 candidate genes and pinpointed multiple biological pathways such as the IRE1 branch of the unfolded protein response, which could play a critical role in clinical susceptibility to L. infantum infection. [ABSTRACT FROM AUTHOR]

To investigate the positive predictive value and false positive risk of copy number variations (CNV's) detected in cell free deoxyribonucleic acid (DNA) from spent culture media for nonviable or aneuploid embryos. Diagnostic/prognostic accuracy study. Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF center. Embryo selection was performed according to the conventional grading, blinded to noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) results. After clinical outcomes were established, spent culture media samples were analyzed. Prognostic accuracy of CNVs according to niPGT-A results to predict nonviability or clinical aneuploidy. One hundred twenty patients completed the study. Interpretations of next-generation sequencing (NGS) profiles were as follows: 7.5% (n = 9) failed quality control; 62.5% (n = 75) no CNVs detected; and 30% (n = 36) abnormal copy number detected. Stratification of abnormal NGS profiles was as follows: 15% (n = 18) whole chromosome and 15% (n = 18) uncertain reproductive potential. An intermediate CNV was evident in 27.8% (n = 5) of the whole chromosome abnormalities. The negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk (RR) for nonviability compared with no detected abnormalities (RR 2.21, 95% CI: 1.66–2.94). No other CNVs were associated with significant differences in the sustained implantation or RRs for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant median absolute pairwise differences between certain subcategories of CNV abnormalities were apparent. Whole chromosome abnormalities were associated with a high positive predictive value and significant RR for nonviability. Embryos associated with other CNVs had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of niPGT-A. clinicaltrials.gov (NCT04732013). [ABSTRACT FROM AUTHOR]

Suicide is a societal and public health concern of global scale. Identifying genetic risk factors for suicide attempt can characterize underlying biology and enable early interventions to prevent deaths. Recent studies have described common genetic variants for suicide-related behaviors. Here, we advance this search for genetic risk by analyzing the association between suicide attempt and uncommon variation exome-wide in a large, ancestrally diverse sample. We sequenced whole genomes of 13,584 soldiers from the Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers), including 979 individuals with a history of suicide attempt. Uncommon, nonsilent protein–coding variants were analyzed exome-wide for association with suicide attempt using gene-collapsed and single-variant analyses. We identified 19 genes with variants enriched in individuals with history of suicide attempt, either through gene-collapsed or single-variant analysis (Bonferroni p adjusted <.05). These genes were CIB2 , MLF1 , HERC1 , YWHAE , RCN2 , VWA5B1 , ATAD3A , NACA , EP400 , ZNF585A , LYST , RC3H2 , PSD3 , STARD9 , SGMS1 , ACTR6 , RGS7BP , DIRAS2 , and KRTAP10-1. Most genes had variants across multiple genomic ancestry groups. Seventeen of these genes were expressed in healthy brain tissue, with 9 genes expressed at the highest levels in the brain versus other tissues. Brains from individuals deceased from suicide aberrantly expressed RGS7BP (p adjusted =.035) in addition to nominally significant genes including YWHAE and ACTR6 , all of which have reported associations with other mental disorders. These results advance the molecular characterization of suicide attempt behavior and support the utility of whole-genome sequencing for complementing the findings of genome-wide association studies in suicide research. [ABSTRACT FROM AUTHOR]