Institute of Genetics

Abstract Researchers’ performance is often evaluated quantitatively through metrics like the number of scientific papers, the number of citations these received, and the H-index, perpetuating the “Publish or Perish” culture. Yet such metrics have inherent biases favoring older, established researchers and fail to account for disciplinary differences or temporal relevance of contributions. To address this inequity, we aimed to create a global, age- and field-adjusted reference for evaluating scientific productivity. We developed a comprehensive worldwide reference database of researchers using publication and citation data from Scopus. The reference dataset includes 507,233 researchers from across the globe and facilitates the calculation of expected values for H-index, annual citations, and recent publications (within the past 5 years) for each percentile in every discipline. To account for disciplinary differences, we incorporated diverse publication types into the analysis tailored to each domain. The benchmarks utilized were stratified by career stage, assessed at each year after a researcher’s first publication. A composite score was developed to rank publication performance into deciles (D1–D10), where D1 represents the highest level of achievement. Importantly, only data from researchers within the same career stage and same scientific domain are used for comparison, ensuring fair and context-sensitive evaluations. To enhance accessibility, we established a web portal ( www.scientometrics.org/scopus ) to facilitate researcher benchmarking. This age- and discipline-normalized international database promotes the application of responsible metrics, offering a robust framework for global scientometric rankings. By providing an online analysis platform, we enable researchers, institutions, and policymakers to determine expected levels of scholarly output at the individual level while fostering fairness and equity in academic evaluation.

Amyloidosis comprises a group of diseases characterized by extracellular deposition of misfolded proteins. Among them, transthyretin amyloidosis (ATTR) stands out due to its increasing prevalence and clinical impact. Genetic testing is essential to confirm the diagnosis, establish prognosis and guide treatment. Since most variants associated with ATTR are single-nucleotide changes, next-generation sequencing (NGS) is the method of choice for their detection. We conducted a descriptive, retrospective-prospective, cross-sectional study to identify variants in the TTR gene in patients with suspected ATTR. A total of 41 patients registered at the National Institute of Medical Genetics and Genomics and referred by the Cardiology Service were included. All were analyzed by next-generation sequencing using a 128-gene cardiomyopathy panel. Forty-one patients were evaluated, of whom 21 met the criteria for final analysis. Five patients (23.8%) carried variants in the TTR gene, while 16 (76.2%) showed no detectable alterations in TTR. Our findings provide a first approximation of the distribution of TTR gene variants in Panamanian patients with suspected transthyretin amyloidosis. The detection of pathogenic variants in this cohort highlights the need to improve diagnostic strategies and to better guide therapeutic decision-making in carriers of these variants.

Primary osteoporosis can be caused by pathogenic variants in multiple genes. Recently, rare heterozygous variants in SGMS2, encoding SGMS2, have been identified to cause early-onset osteoporosis or more severe skeletal dysplasia. The incidence of pathogenic SGMS2 variants and their consequent clinical features, however, remain limited. This study aimed to identify the prevalence and nature of SGMS2 variants in Finnish patients with genetically undiagnosed idiopathic early-onset osteoporosis. All eleven exons and exon-intron boundaries of SGMS2 were sequenced. In a cohort of 44 patients (42 females and two males, median age at the time of recruitment 60 years, range 25-76 years), we identified one rare heterozygous missense variant (c.715T>C, p.Phe239Leu) and three intronic variants with unknown functional consequences; no pathogenic or likely pathogenic variants were found. Our results suggest that pathogenic variants in SGMS2 are not a common cause of early-onset idiopathic osteoporosis in Finnish patients. Further studies in larger cohorts and variable skeletal phenotypes are needed to increase our understanding of the role of SGMS2 in skeletal fragility.

Abstract Ancient DNA is a valuable data source for the understanding of our past. However, to effectively interpret this data, it is essential to know the age of the samples from which the DNA is obtained. Although the field of palaeogenomics has been recognised for its robust open data sharing practices, dating information associated with analysed samples is not reported consistently across palaeogenomic studies, nor is it included as metadata in most genetic data repositories. Here, we describe the addition of standardised precise dating information for ancient microbial genomes into the AncientMetagenomeDir metadata repository of published ancient metagenomic samples. This extension currently includes dating information for over 700 ancient microbial genomic datasets, of which 333 are dated using historical, contextual, or stratigraphic methods, and 405 are radiocarbon dated. We quantitatively assess the quality of radiocarbon date reporting and find that, despite established reporting conventions, radiocarbon dating information is often reported inconsistently across ancient metagenomic studies. This new resource provides ancient microbial researchers with standardised dating information that facilitates more accurate and consistent analysis of metagenomic sequencing data. The dataset also highlights the need for greater standardisation of radiocarbon date reporting in original publications in order to allow effective reuse of this and future ancient microbial data.

Abstract While significant progress has been made in understanding the genetic architecture of ageing in model organisms, our understanding of human ageing remains limited. We performed a multi-tissue Transcriptome-wide association study (TWAS) on human lifespan, integrating GWAS data from >1 million parental lifespans with gene expression prediction models derived from reference transcriptomic datasets; followed by replication using healthspan and longevity phenotypes as additional readouts of ageing. The TWAS uncovered 563 significant gene associations, of which 139 replicated. TOMM40 , encoding a component of the mitochondrial outer membrane translocase that is fundamental for mitochondrial function, had the strongest association with parental lifespan and longevity and was fine-mapped as a putatively causal lifespan gene at the APOE-TOMM40 region. Uniquely in our study, we identified fly orthologues of replicating genes and examined if modulating their expression impacts Drosophila longevity. The nine novel associations with all three ageing outcomes included COASY, encoding Coenzyme A synthase. Knocking down its fly orthologue, Ppat-dpck , resulted in significant lifespan extension in flies. Hence, in addition to discovering new genes associated with human ageing, by combining human TWAS with experimental Drosophila work, we provide evidence for the role of COASY ( Ppat-dpck ) in ageing across species. Significance statement Extensive research on ageing has been conducted in Drosophila and C.elegans due to their short lifespan and experimental tractability. However, in human genetic research, only a few loci have been consistently replicated. To bridge this gap, we conducted a transcriptome-wide association study (TWAS) followed by experimental validation in Drosophila . TWAS revealed 139 significant and replicating gene associations, including COASY. Knockdown of its fly orthologue ( Ppat-dpck ) significantly extended fly lifespan, validating its roles in ageing across species. Thus, integrating multiple ageing outcomes through TWAS in human genetic research can uncover robust associations and highlight genes involved in fundamental ageing mechanisms.

The extraction of plant essential nutrients from extraterrestrial regolith will be necessary to ensure the sustainability of lunar and martian agriculture. An essential instrument of these outposts will be bioregenerative life support systems (BLiSS) that attempt to fully recycle nutrients from organic wastes. While BLiSS may not be fully efficient and lead to a reduction in the quantity of some elements, it is necessary to explore if regolith can be used to fortify the composition of BLiSS effluent. Lunar (JSC-1A) and martian simulants (MGS-1) were reacted with a high-fidelity BLiSS effluent from NASA's Kennedy Space Center (KSC) in a 24 h batch experiment and compared to reactions with an inorganic nutrient solution and water. Net sorption and dissolution of elements were determined by quantification of reacting solutions using inductively coupled plasma-optical emission spectroscopy (ICP-OES), with P demonstrating Langmuir and Zn and K demonstrating Freundlich sorption isotherms. The lunar simulant desorbed sizeable quantities of S, followed by Ca and Mg, while the martian simulant desorbed S, followed by Mg, Ca, and Na. Elemental bonding of C, N, P, and Ca was observed on the simulant solid phase with X-ray photoelectron spectroscopy (XPS) after reaction with BLiSS solution. Minerals after experimentation were observed using scanning electron microscope-electron dispersive spectroscopy (SEM-EDS), revealing pitting in JSC-1A and covering of nanoparticles in MGS-1. There were marked differences between the reactions of the inorganic nutrient solution compared to BLiSS effluent, indicating the necessity to study high-fidelity solutions over single-element model systems. Overall, lunar and martian regoliths contain highly soluble components that may fortify BLiSS effluents with valuable metals and plant essential nutrients.

Abstract Deubiquitinases (DUBs) remove ubiquitin modifications from proteins in a substrate- or linkage-selective manner and regulate numerous cell-biological processes, including endocytosis. By performing homology-agnostic bioinformatical screens for undescribed deubiquitinase classes, we identified the plant-specific DUC ( d e u biquitinase with C 2) family, whose members are highly selective for cleaving K63-linked ubiquitin chains. The crystal structure of the Arabidopsis member AtDUC1 reveals that DUC enzymes display a papain-like fold with a characteristic DUB-like active site, despite the apparent absence of sequence similarity to other deubiquitinase families. The K63 linkage specificity is attributed to the recognition of both distal and proximal ubiquitin units via highly conserved contact residues. Arabidopsis DUC members localize to the plasma membrane by virtue of their lipid-binding C2-like domains. In protoplast experiments, all three Arabidopsis DUC enzymes demonstrate the capacity to stabilize an endocytotic model cargo at the plasma membrane, a process that requires both the C2-mediated membrane association and catalytic DUB activity.

Inflammation and immune evasion promote tumorigenesis and progression. Elevated systemic inflammation response index (SIRI) is associated with poor progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients. Low Human Leukocyte Antigen-DR (HLA-DR) expression on monocytes is also associated with poor prognosis in NSCLC. We aimed to investigate the relationship between these two indicators and develop a predictive model based on them. SIRI was calculated and monocyte HLA-DR expression was measured by flow cytometry in 58 advanced (stage IIIB-IV) NSCLC patients. The log-rank test and multivariate Cox proportional hazard regression model were used for analysis. We confirmed that both high SIRI and low monocyte HLA-DR expression were associated with poor PFS and OS, respectively. We found a significant inverse correlation between SIRI and monocyte HLA-DR expression. In the multivariable Cox regression model, both SIRI and monocyte HLA-DR expression were identified as independent prognostic markers for PFS and OS. We also developed a nomogram for predicting PFS and OS. In conclusion, we demonstrated that the systemic inflammation response of advanced NSCLC patients, estimated by SIRI, was associated with reduced HLA-DR expression on circulating monocytes, which may influence their antigen-presenting function. Consequently, the integration of these two biomarkers into one prognostic model improves short term survival prediction in advanced NSCLC. To our knowledge, this is the first integration of SIRI and HLA-DR into a combined prognostic nomogram.