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At least 595 records · Page 33Linked to original sources

Integrated economic-ecological analysis and evaluation of management strategies on nutrient abatement in the Rhine basin.

Management of river basins involves the making of informed choices about the desired levels of economic activities and ecosystem functioning in the catchment. Information on the economic and ecological effects of measures as well as their spatial distribution is therefore needed. This paper proposes the following instruments to support decision-making in river basins: (1) the linking of models and indicators to describe the economic and ecological effects of management actions and their spatial distribution and (2) an extended evaluation framework that aims to evaluate management actions on three objectives for sustainable river management. These are cost-effectiveness, spatial equity, and environmental quality. This paper illustrates the potential of these instruments for river basin management by a case-study on nutrient management in the Rhine basin. In this case-study four nutrient abatement strategies are formulated, based on policies of the International Commission for the Protection of the Rhine and the North Sea Commission. These strategies are analysed and evaluated on their contribution to the three management objectives. Results show that none of these strategies score highest on cost-effectiveness, spatial equity and environmental quality simultaneously. It appears that cost-effectiveness is in conflict with environmental quality, whereas spatial equity and cost-effectiveness show quite close correspondence. This means that a trade-off has to be made between costs and spatial equity on the one hand, and environmental standards on the other hand. This paper offers a framework to make these trade-offs more explicit and provides quantitative information on cause-effect relationships, economic and environmental effects and the spatial distribution of these effects for various management strategies. This information can be particularly useful in the development of compromises required to establish international agreement and co-operation.

Conservation of Natural Resources↗

Genomic and integrative based progression biomarker discovery in adult sepsis: toward clinical stratification and precision medicine.

Sepsis is a life-threatening syndrome characterized by a heterogeneous host response to infection that remains a major cause of mortality worldwide. Current clinical scoring systems capture organ dysfunction but fail to reflect the underlying biological diversity, limiting their utility for patient stratification and targeted therapy. This review provides a comprehensive overview of molecular biomarker approaches used to predict sepsis course and prognosis in adult patients, covering genetic, transcriptomic, proteomic, and integrative strategies up to May 2026. Here, we summarize findings from genetic association studies, along with analyses based on polygenic risk scores to aggregate genetic effects, Mendelian randomization, and rare-variant sequencing approaches. We also review transcriptomic and proteomic strategies for endotyping, and diagnostic and prognostic discrimination. Lastly, we discuss how multi-omics integration is emerging as a promising framework to assist in distinguishing causal therapeutic targets from non-causal biomarkers. We also address the challenges that still constrain clinical translation towards precision medicine.

Biomarker↗

Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.

OBJECTIVES: Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. METHODS: We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. RESULTS: SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. CONCLUSIONS: Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.

Humans↗

The development of discourse referencing in Cantonese-speaking children.

The ability to make clear reference in connected discourse was examined in children learning Cantonese, a Chinese language where noun phrase constituents, whatever their grammatical role, are omissible from sentences under discourse conditions that are not well-understood. Forty-three typically developing children aged 3 ; 0, 5 ; 0, 7 ; 0 and 12 ; 0 told 16 stories based on picture sequences. A panel of adult native Cantonese speakers was asked to judge the referential adequacy of each child's stories by identifying the character the child was talking about in 32 targeted referential acts. The targeted acts were of three sorts: MAINTENANCE of a known character, INTRODUCTION of a second new character, and REINTRODUCTION of a known character. Reference was judged to be adequate when 3 out of 4 'listeners' could successfully identify the character. Children's referential expressions were most adequate for Maintenance, less adequate for Introduction, and least adequate for Reintroduction. The twelve- and seven-year-olds approached ceiling on all three functions. The five-year-olds scored poorly on Reintroduction, and the three-year-olds failed both Introduction and Reintroduction, despite knowledge of at least one of the possible linguistic forms required for these acts as evidenced in a sentence imitation task. Viewed within the framework of Levelt's (1989) discourse model, the data improve our understanding of the developmental period during which children learn to make appropriate presuppositions about the listener's knowledge and attentional states.

Child↗

Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles.

Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds predisposed to immune-mediated diseases. Because dogs co-express DLA-DR and DLA-DQ, the MHC class II Ab clone YKIX334.2 was validated to be DLA-DR-specific, enabling allele-selective immunoaffinity purification of DLA-DR molecules from homozygous DLA-DR15 and DLA-DR12 donor spleens. Mass spectrometry and GibbsCluster motif deconvolution of 838 DLA-DR15-associated and 644 DLA-DR12-associated peptides eluted from their respective peptide-binding grooves revealed distinct allele-specific binding motifs, with characterization of anchor residue preferences, peptide-length distributions, cross-species comparisons with human and murine MHC class II motifs, and source protein composition of the eluted self-peptidome. To evaluate the translational utility of these motifs, recombinant DLA-DR15 and DLA-DR12 molecules were used to screen rabies virus glycoprotein and nucleoprotein peptide libraries via fluorescence-based peptide competition assays, identifying high-affinity candidate binders for both alleles. Spearman rank correlation between immunopeptidomics-derived position-specific scoring matrix scores and peptide competition assay rankings demonstrated modest associations, consistent with these approaches capturing complementary dimensions of peptide-MHC class II interaction. Ultimately, these findings establish what we believe is the first allele-specific peptide-binding motif framework for canine MHC class II, providing a foundation for DLA-allele-informed CD4+ T-cell epitope discovery studies and Ag-specific immune response characterization in the dog.

Animals↗

A supersecondary structure library and search algorithm for modeling loops in protein structures.

We present a fragment-search based method for predicting loop conformations in protein models. A hierarchical and multidimensional database has been set up that currently classifies 105,950 loop fragments and loop flanking secondary structures. Besides the length of the loops and types of bracing secondary structures the database is organized along four internal coordinates, a distance and three types of angles characterizing the geometry of stem regions. Candidate fragments are selected from this library by matching the length, the types of bracing secondary structures of the query and satisfying the geometrical restraints of the stems and subsequently inserted in the query protein framework where their fit is assessed by the root mean square deviation (r.m.s.d.) of stem regions and by the number of rigid body clashes with the environment. In the final step remaining candidate loops are ranked by a Z-score that combines information on sequence similarity and fit of predicted and observed phi/psi main chain dihedral angle propensities. Confidence Z-score cut-offs were determined for each loop length that identify those predicted fragments that outperform a competitive ab initio method. A web server implements the method, regularly updates the fragment library and performs prediction. Predicted segments are returned, or optionally, these can be completed with side chain reconstruction and subsequently annealed in the environment of the query protein by conjugate gradient minimization. The prediction method was tested on artificially prepared search datasets where all trivial sequence similarities on the SCOP superfamily level were removed. Under these conditions it is possible to predict loops of length 4, 8 and 12 with coverage of 98, 78 and 28% with at least of 0.22, 1.38 and 2.47 A of r.m.s.d. accuracy, respectively. In a head-to-head comparison on loops extracted from freshly deposited new protein folds the current method outperformed in a approximately 5:1 ratio an earlier developed database search method.

Algorithms↗

Computational modeling of human genetic variants in mice.

Mouse models represent a powerful platform to study genes and variants associated with human diseases. While genome editing technologies have increased the rate and precision of model development, predicting and installing specific types of mutations in mice that mimic the native human genetic context is complicated. Computational tools can identify and align orthologous wild-type genetic sequences from different species; however, predictive modeling and engineering of equivalent mouse variants that mirror the nucleotide and/or polypeptide change effects of human variants remains challenging. Here, we present H2M (human-to-mouse), a computational pipeline to analyze human genetic variation data to systematically model and predict the functional consequences of equivalent mouse variants. We show that H2M can integrate mouse-to-human and paralog-to-paralog variant mapping analyses with precision genome editing pipelines to devise strategies tailored to model specific variants in mice. We leveraged these analyses to establish a database containing > 3 million human-mouse equivalent mutation pairs, as well as in silico-designed base and prime editing libraries to engineer 4,944 recurrent variant pairs. Using H2M, we also found that predicted pathogenicity and immunogenicity scores were highly correlated between human-mouse variant pairs, suggesting that variants with similar sequence change effects may also exhibit broad interspecies functional conservation. Overall, H2M fills a gap in the field by establishing a robust and versatile computational framework to identify and model homologous variants across species while providing key experimental resources to augment functional genetics and precision medicine applications. The H2M database (including software package and documentation) can be accessed at https://human2mouse.com.

Journal Article↗

Validating an instrument for selecting interventions to change physician practice patterns: a Michigan Consortium for Family Practice Research study.

OBJECTIVES: The goal of this study was to develop a psychometric instrument that classified physiciansamprsquo response styles to new information as seekers, receptives, traditionalists, or pragmatists. This classification was based on specific combinations of 3 scales: (a) belief in evidence vs experience as the basis of knowledge, (b) willingness to diverge from common or previous practice, and (c) sensitivity to pragmatic concerns of practice. The instrument will help focus efforts to change practice more accurately. STUDY DESIGN: This was a cross-sectional study of physician responses to a psychometric instrument. Paper-and-pencil survey forms were distributed to 3 waves of physicians, with revision for improved internal consistency at each iteration. POPULATION: Participants were 1393 primary care physicians at continuing education events in the Midwest or at primary care clinic sites in the Veteransamprsquo Health Administration system. OUTCOMES MEASURED: Internal consistency was measured by factor analysis with orthogonal rotation and Cronbachamprsquos alpha. RESULTS: A total of 1287 usable instruments were returned (106, 1120, and 61 in the 3 iterations, respectively), representing approximately three fourths of distributed forms. Final scale internal consistencies were a = 0.79, b = 0.74, and c = 0.68. The patterns of scores on the 3 scales were consistent with the predictions of the theoretical scheme of physician types. The "seeker" type was the rarest, at fewer than 3%. CONCLUSIONS: It is possible to reliably classify physicians into categories that a theoretical framework predicts will respond differently to different interventions for implementing guidelines and translating research findings into practice. The next step is to demonstrate that the classification predicts physician practice behavior.

Adult↗

Oncology nurses' knowledge of graft-versus-host disease in bone marrow transplant patients.

Graft-versus-host disease (GVHD) is a serious complication of allogenic bone marrow transplantation. A descriptive study was conducted to determine oncology nurses' knowledge of GVHD in bone marrow transplant patients. The research question was: Do oncology nurses who participate in continuing education programs and read journal articles on GVHD have increased knowledge, as compared with oncology nurses who do not participate in these activities? Seventy-eight nurses completed a demographic data form and a GVHD questionnaire developed by the investigators (r = 0.71). Multiple regression analysis determined the relationships between independent and dependent variables. An analysis of variance determined a significant difference between the mean scores associated with the identified learning activities (F = 3.61, p less than 0.05). Continuing education activities and reading of journal articles were associated with higher knowledge scores (R2 = 0.1052, p less than 0.05). Many oncology nurses have no formal education in bone marrow transplantation and limited clinical experience with GVHD. Additional work must be done to determine if some oncology nurses practice from a weak theoretical framework and have limited rationales for their nursing actions. Further research, instrument development, and a teaching protocol on GVHD will enhance the nursing care needed by the patient with GVHD.

Bone Marrow Transplantation↗

[Early child morbidity and late development following primary abdominal cesarean section in breech presentation near term].

This study concerns the results obtained in respect of early morbidity and late development of 115 and 57 children, respectively, born between 1978 and 1983, who had been delivered by primary low cervical Caesarean section shortly before term. Early morbidity of the 115 children was analysed taking into consideration the risk factors, such as premature rupture, gestation diabetes, EPH gestosis, condition following Caesarean section, abnormal amnioscopic and antepartal cardiotocographic findings, as well as the methods of anaesthesia employed. In the study on late development 57 children between 1 1/4 and 6 years of age were followed up and examined with regard to several faculties (social contact, fine motoricity and adaptation, speech and gross motoricity) according to the Denver Developmental Screening Test. Children with abnormal findings were subjected to special examination. Children with abnormal findings were also subjected to a positional test according to Vojta and to the Munich functional developmental diagnosis after Hellbrüge et al. While employing physiotherapy after Bobath and early rehabilitation training by the parents, these children were followed up at regular intervals. There was no clinically relevant acidosis in the group of 115 newborn. A total of 44 newborn (38%) displayed slight to medium enhanced acidity (pH value, umbilical artery: 7.20 to 7.29) according to the stage classification after Saling and Wulf. Slight to medium acidosis (umbilical artery pH 7.10 to 7.19) was seen in 3 cases only (2.6%). In 112 newborn we found a correlation between the good Apgar score values (7-10) and normal acidity in the umbilical artery blood (act. umbilical artery pH greater than or equal to 7.30). In the remaining 3 newborn with lower Apgar scores (3-6) there was no acidosis in the umbilical artery blood. In the follow-up group (57 cases) we found one child with psychomotor retardation of speech (disturbed articulation and reduced vocabulary) and 6 children with slight motor disturbances in the early developmental stage. These disturbances were recorded as slight central disturbances of coordination according to Vojta within the framework of early diagnosis. Four of these children received early treatment according to Bobath. When they were between 1 and 1 1/2 years of age, all the 4 children showed normalisation of motoricity during the follow-up checks. The other two children displayed spontaneous regression of the mild central disturbance of coordination when they were 5 and 6 months of age.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗

A multiple-feature framework for modelling and predicting transcription factor binding sites.

MOTIVATION: The identification of transcription factor binding sites in promoter sequences is an important problem, since it reveals information about the transcriptional regulation of genes. For analysing transcriptional regulation, computational approaches for predicting putative binding sites are applied. Commonly used stochastic models for binding sites are position-specific score matrices, which show weak predictive power. RESULTS: We have developed a probabilistic modelling approach, which allows to consider diverse characteristic binding site properties to obtain more accurate representations of binding sites. These properties are modelled as random variables in Bayesian networks, which are capable of dealing with dependencies among binding site properties. Cross-validation on several datasets shows improvements in the false positive error rate and the significance (P-value) of true binding sites.

Algorithms↗

Combining several screening tests: optimality of the risk score.

The development of biomarkers for cancer screening is an active area of research. While several biomarkers exist, none is sufficiently sensitive and specific on its own for population screening. It is likely that successful screening programs will require combinations of multiple markers. We consider how to combine multiple disease markers for optimal performance of a screening program. We show that the risk score, defined as the probability of disease given data on multiple markers, is the optimal function in the sense that the receiver operating characteristic (ROC) curve is maximized at every point. Arguments draw on the Neyman-Pearson lemma. This contrasts with the corresponding optimality result of classic decision theory, which is set in a Bayesian framework and is based on minimizing an expected loss function associated with decision errors. Ours is an optimality result defined from a strictly frequentist point of view and does not rely on the notion of associating costs with misclassifications. The implication for data analysis is that binary regression methods can be used to yield appropriate relative weightings of different biomarkers, at least in large samples. We propose some modifications to standard binary regression methods for application to the disease screening problem. A flexible biologically motivated simulation model for cancer biomarkers is presented and we evaluate our methods by application to it. An application to real data concerning two ovarian cancer biomarkers is also presented. Our results are equally relevant to the more general medical diagnostic testing problem, where results of multiple tests or predictors are combined to yield a composite diagnostic test. Moreover, our methods justify the development of clinical prediction scores based on binary regression.

Bayes Theorem↗

Toward objective and quantitative evaluation of imaging systems using images of phantoms.

The use of imaging phantoms is a common method of evaluating image quality in the clinical setting. These evaluations rely on a subjective decision by a human observer with respect to the faintest detectable signal(s) in the image. Because of the variable and subjective nature of the human-observer scores, the evaluations manifest a lack of precision and a potential for bias. The advent of digital imaging systems with their inherent digital data provides the opportunity to use techniques that do not rely on human-observer decisions and thresholds. Using the digital data, signal-detection theory (SDT) provides the basis for more objective and quantitative evaluations which are independent of a human-observer decision threshold. In a SDT framework, the evaluation of imaging phantoms represents a "signal-known-exactly/background-known-exactly" ("SKE/ BKE") detection task. In this study, we compute the performance of prewhitening and nonprewhitening model observers in terms of the observer signal-to-noise ratio (SNR) for these "SK E/BKE" tasks. We apply the evaluation methods to a number of imaging systems. For example, we use data from a laboratory implementation of digital radiography and from a full-field digital mammography system in a clinical setting. In addition, we make a comparison of our methods to human-observer scoring of a set of digital images of the CDMAM phantom available from the internet (EUREF-European Reference Organization). In the latter case, we show a significant increase in the precision of the quantitative methods versus the variability in the scores from human observers on the same set of images. As regards bias, the performance of a model observer estimated from a finite data set is known to be biased. In this study, we minimize the bias and estimate the variance of the observer SNR using statistical resampling techniques, namely, "bootstrapping" and "shuffling" of the data sets. Our methods provide objective and quantitative evaluation of imaging systems with increased precision and reduced bias.

Algorithms↗

Genetic and physical mapping of the bovine X chromosome.

Three hundred eighty reciprocal backcross and F(2) full sib progeny from 33 families produced by embryo transfer from 77 Angus (Bos taurus), Brahman (Bos indicus), and F1 parents and grandparents were used to construct genetic maps of the bovine X and Y chromosomes. Ml individuals were scored for 15 microsatellite loci, with an average of 608 informative meioses per locus. The length of the bovine X chromosome genetic map was 118.7 cM (female only) and of the pseudoautosomal region was 13.0 cM (male only). The 15-marker framework map in Kosambi centimorgans is [BM6017-6.1 -TGLA89-35.8-TEXAN13-3.4-TGLA128-1.3 -BM2713 -21.1 -BM4604-2.4-BR215 - 12.9-TGLA68-10.0-BM4321 - 1.0-HEL14-4.9-TGLA15-2.3-INRA12O- 12.5-TGLA325- 1.6-MAF45-3.2-INRA3O], with an average interval of 7.91 cM. Clones containing pseudoautosomal or sex-linked microsatellites were isolated from a bovine bacterial artificial chromosome library and were physically mapped to bovine metaphase chromosomes by fluorescence in situ hybridization to orient the X and Y chromosome maps. BAC57, containing the pseudoautosomal microsatellite INRA3O, mapped to the distal end of the long arm of the X chromosome at q42-ter and to the short arm of the Y chromosome at p13-ter. This confirms the published assignment of this region to Ypl2-ter, but challenges the published assignment of Xpl4-ter and thus reorients the X chromosome physical map. BAC2O4, containing the X-linked microsatellite BM4604, mapped to the middle of the long arm of the X chromosome at q26-q31. The position of the physically mapped markers indicates either a lack of microsatellite markers for a large (30 to 50 cM) region of the short arm of the X chromosome or heterogeneity of recombination along the X chromosome.

Animals↗

Predicting risk of ischemic stroke: A transformer model using genomic data.

BACKGROUND AND OBJECTIVE: Ischemic stroke is a leading cause of mortality and long-term disability worldwide. Genetic factors contribute to IS susceptibility, yet conventional polygenic risk score approaches are primarily based on additive effects and may not fully capture non-linear relationships or positional context and interactions among genetic variants. This study aimed to develop and evaluate a transformer-based genomic model incorporating position-wise genotype embedding for IS risk prediction. METHODS: We conducted a genome-wide association study using the UK Biobank dataset to identify IS-associated loci. Gene prioritisation was subsequently performed using tissue-specific expression quantitative trait locus-based Mendelian randomisation and colocalization analyses in whole blood and brain cortex. We then developed a transformer-based model that encoded genotype and SNP-position information using a position-wise embedding layer. Model performance was evaluated across three UK Biobank control definitions and externally assessed in the independent All of Us cohort. Performance metrics included the area under the receiver operating characteristic curve (AUROC), precision, recall, and F1 score. RESULTS: Across the three UK Biobank control definitions, the proposed method achieved the numerically highest discrimination among the evaluated models, with AUROCs of 0.8109, 0.7843, and 0.7468 using MRF-negative, combined, and MRF-positive controls, respectively. In the external All of Us cohort, the proposed method achieved an AUROC of 0.7251 and retained the highest AUROC among the evaluated models. In a separate incident-stroke survival analysis, medium- and high-score groups had hazard ratios of 1.13 and 1.21, respectively, relative to the low-score group. A total of 18 IS-associated loci were identified. Among the tissue-specific MR results, EDEM2 in the brain cortex remained significant after Bonferroni correction, while DCHS2 showed a nominal association. CONCLUSIONS: The proposed transformer-based framework provides a genomic modelling approach that achieved the highest discrimination among the evaluated models in this study and retained comparative performance in an independent external cohort. In further applications, integrating this genomic framework with conventional clinical, lifestyle, and environmental risk factors may support more comprehensive and personalised IS risk assessment. Prospective, population-representative, and multi-ancestry validation will be important to establish its potential role in future prevention-oriented risk management.

Genomics and bioinformatics↗

Assessing the clinical impact of prognostic factors: when is "statistically significant" clinically useful?

Very few tumor markers have been recommended for routine clinical care of patients with breast cancer. A framework to determine the clinical utility of tumor markers is required. In a previous publication, a "Tumor Marker Utility Grading System" (TMUGS) was proposed. TMUGS included a semi-quantitative grading scale (0-3+) which can be used to assign a score to a given tumor marker for a given outcome. Only those markers that are felt to be sufficiently strong to influence a therapeutic decision that results in improved clinical outcome for the patient are recommended. The studies from which data are used to assign a TMUGS grade can be placed into one of five Levels of Evidence (LOE). An extension of TMUGS ("TMUGS-Plus") is now proposed in which the relative strength of a prognostic or predictive factor can be estimated and expressed in terms of a risk ratio (RR) for prognostic factors or benefit ratio (BR) for predictive factors. Three categories of prognostic factors and three categories of predictive factors are proposed (strong, moderate, and weak). It is recommended that only LOE type I studies (prospective, highly powered studies of the tumor marker, or meta-analysis of LOE II or III datasets), be used to estimate the RR or BR of a given factor. Finally, a matrix, based on assumptions of acceptable absolute benefits relative to risks, is proposed in which any given tumor marker can be assessed for its clinical utility. TMUGS-Plus should aid in the assessment of published data regarding clinical utility of tumor markers. Perhaps more important, clinical investigators can use TMUGS-Plus to design tumor marker studies that will fulfill criteria for clinical utility, resulting in more rapid acceptance of tumor markers for routine clinical use.

Biomarkers, Tumor↗

DIVAS: an R package for identifying shared and individual variations of multiomics data.

MOTIVATION: Multiomics data integration aims to identify biological patterns shared across molecular modalities. Most existing methods detect either jointly shared variation, across all modalities, or individual variation, unique to a single modality, but overlook partially shared variation, shared by only a subset of modalities. This is a critical limitation, because many biological mechanisms manifest in some but not all molecular modalities. RESULTS: We present an open-source R package implementing data integration via analysis of subspaces (DIVAS), a framework for systematically identifying jointly shared, partially shared and individual variations across multiple data types. DIVAS combines angle-based subspace analysis with inference through rotational bootstrap, hierarchically searching all combinations of modalities to decompose multiomics data into interpretable components with scores and loadings. In simulations with a known sharing structure, DIVAS recovered every component across a wide range of noise levels, whereas existing methods did not. Applied to multi-modal COVID-19 data, it reveals partially shared immune and metabolic dysregulation patterns underpinning disease severity that conventional approaches would miss. AVAILABILITY AND IMPLEMENTATION: DIVAS is available at https://github.com/ByronSyun/DIVAS, with documentation and vignettes. The COVID-19 case study vignette is available at https://byronsyun.github.io/DIVAS_COVID19_CaseStudy/.

Multiomics↗

ROCR: visualizing classifier performance in R.

UNLABELLED: ROCR is a package for evaluating and visualizing the performance of scoring classifiers in the statistical language R. It features over 25 performance measures that can be freely combined to create two-dimensional performance curves. Standard methods for investigating trade-offs between specific performance measures are available within a uniform framework, including receiver operating characteristic (ROC) graphs, precision/recall plots, lift charts and cost curves. ROCR integrates tightly with R's powerful graphics capabilities, thus allowing for highly adjustable plots. Being equipped with only three commands and reasonable default values for optional parameters, ROCR combines flexibility with ease of usage. AVAILABILITY: http://rocr.bioinf.mpi-sb.mpg.de. ROCR can be used under the terms of the GNU General Public License. Running within R, it is platform-independent. CONTACT: tobias.sing@mpi-sb.mpg.de.

Computer Graphics↗