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PubMed2006

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.

Cystic ovarian follicles (COF) are an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Due to the complexity of the disorder and the heterogeneity of the clinical signs, a clear definition is lacking. A follicle becomes cystic when it fails to ovulate and persists on the ovary. Despite an abundance of literature on the subject, the exact pathogenesis of COF is unclear. It is generally accepted that disruption of the hypothalamo-pituitary-gonadal axis, by endogenous and/or exogenous factors, causes cyst formation. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. In addition, several factors can influence GnRH/LH release at the hypothalamo-pituitary level. At the ovarian level, cellular and molecular changes in the growing follicle may contribute to anovulation and cyst formation, but studying follicular changes prior to cyst formation remains extremely difficult. Differences in receptor expression between COF and dominant follicles may be an indication of the pathways involved in cyst formation. The genotypic and phenotypic link of COF with milk yield may be attributed to negative energy balance and the associated metabolic and hormonal adaptations. Altered metabolite and hormone concentrations may influence follicle growth and cyst development, both at the level of the hypothalamus-pituitary and the ovarian level.

Animals↗
PubMed2004

Crystal structures of Escherichia coli uridine phosphorylase in two native and three complexed forms reveal basis of substrate specificity, induced conformational changes and influence of potassium.

Uridine phosphorylase (UP) is a key enzyme in the pyrimidine salvage pathway that catalyses the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. Inhibiting liver UP in humans raises blood uridine levels and produces a protective effect ("uridine rescue") against the toxicity of the chemotherapeutic agent 5-fluorouracil without reducing its antitumour activity. We have investigated UP-substrate interactions by determining the crystal structures of native Escherichia coli UP (two forms), and complexes with 5-fluorouracil/ribose 1-phosphate, 2-deoxyuridine/phosphate and thymidine/phosphate. These hexameric structures confirm the overall structural similarity of UP to E.coli purine nucleoside phosphorylase (PNP) whereby, in the presence of substrate, each displays a closed conformation resulting from a concerted movement that closes the active site cleft. However, in contrast to PNP where helix segmentation is the major conformational change between the open and closed forms, in UP more extensive changes are observed. In particular a swinging movement of a flap region consisting of residues 224-234 seals the active site. This overall change in conformation results in compression of the active site cleft. Gln166 and Arg168, part of an inserted segment not seen in PNP, are key residues in the uracil binding pocket and together with a tightly bound water molecule are seen to be involved in the substrate specificity of UP. Enzyme activity shows a twofold dependence on potassium ion concentration. The presence of a potassium ion at the monomer/monomer interface induces some local rearrangement, which results in dimer stabilisation. The conservation of key residues and interactions with substrate in the phosphate and ribose binding pockets suggest that ribooxocarbenium ion formation during catalysis of UP may be similar to that proposed for E.coli PNP.

Catalytic Domain↗
PubMed2026

pmultiqc: An Open-Source, Lightweight, and Metadata-Oriented QC Reporting Library for MS Proteomics.

The increasing scale and complexity of proteomics data demand robust, scalable, and interpretable quality control (QC) frameworks to ensure data reliability and reproducibility. Here, we present pmultiqc, an open-source Python package that standardizes and generates web-based QC reports across multiple proteomics data analysis platforms. Built on top of the widely adopted MultiQC framework, pmultiqc offers specialized modules tailored to mass spectrometry workflows, with full initial support for quantms, DIA-NN, MaxQuant/MaxDIA, FragPipe, and mzIdentML/mzML-based pipelines. The package computes a wide range of QC metrics, including raw intensity distributions, identification rates, retention time consistency, and missing value patterns, and presents them in interactive, publication-ready reports. By leveraging sample metadata in the Sample and Data Relationship Format format, pmultiqc enables metadata-aware QC and introduces, for the first time in proteomics, QC reports and metrics guided by standardized sample metadata. Its modular architecture allows easy extension to new workflows and formats. Alongside comprehensive documentation and examples for running pmultiqc locally or integrated into existing workflows, we offer a cloud-based service that enables users to generate QC reports from their own data or public PRIDE datasets.

Proteomics↗
PubMed2002

T-cell engagement of dendritic cells rapidly rearranges MHC class II transport.

Assembly of major histocompatibility complex (MHC) molecules, which present antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic reticulum; once assembled, these molecules travel from the endoplasmic reticulum to their final destination. MHC class II molecules follow a route that takes them by means of the endocytic pathway, where they acquire peptide, to the cell surface. The transport of MHC class II molecules in 'professional' antigen-presenting cells (APCs) is subject to tight control and responds to inflammatory stimuli such as lipopolysaccharide. To study class II transport in live APCs, we replaced the mouse MHC class II gene with a version that codes for a class II molecule tagged with enhanced green fluorescent protein (EGFP). The resulting mice are immunologically indistinguishable from wild type. In bone-marrow-derived dendritic cells, we observed class II molecules in late endocytic structures with transport patterns similar to those in Langerhans cells observed in situ. We show that tubular endosomes extend intracellularly and polarize towards the interacting T cell, but only when antigen-laden dendritic cells encounter T cells of the appropriate specificity. We propose that such tubulation serves to facilitate the ensuing T-cell response.

Animals↗
PubMed2025

Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome.

Adipocyte hypertrophy during obesity triggers chronic inflammation, leading to metabolic disorders. However, the role of adipocyte-specific inflammatory signaling in metabolic syndrome remains unclear. The linear ubiquitin chain assembly complex, LUBAC, is an E3-ligase that generates nondegradative linear ubiquitination (Lin-Ub). LUBAC regulates NF-κB/MAPK-driven inflammation and prevents cell death triggered by immune receptors like TNF receptor-1. Here, we show that mice lacking HOIP, the Lin-E3 ligase catalytic subunit of LUBAC, in adipocytes (HoipA-KO) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Mechanistically, loss of HOIP attenuates TNF-induced NF-κB activation and promotes cell death in human adipocytes. Inhibiting caspase-8-mediated cell death is sufficient to prevent lipodystrophy and MASLD in HoipA-KO obese mice. HOIP expression in adipose tissue positively correlates with metabolic fitness in obese individuals. Overall, our findings reveal a fundamental developmental role for Lin-Ub in adipocytes by mitigating cell death-driven adipose tissue inflammation and protecting against obesity-related metabolic syndrome.

Animals↗
PubMed2006

Zonal organization of the mouse flocculus: physiology, input, and output.

The zones of the flocculus have been mapped in many species with a noticeable exception, the mouse. Here, the functional map of the mouse was constructed via extracellular recordings followed by tracer injections of biotinylated-dextran-amine and immunohistochemistry for heat-shock protein-25. Zones were identified based on the Purkinje cell complex spike modulation occurring in response to optokinetic stimulation. In zones 1 and 3 Purkinje cells responded best to rotation about a horizontal axis oriented at 135 degrees ipsilateral azimuth, whereas in zones 2 and 4 they responded best to rotation about the vertical axis. The tracing experiments showed that Purkinje cells of zone 1 projected to the parvicellular part of lateral cerebellar nucleus and superior vestibular nucleus, while Purkinje cells of zone 3 projected to group Y and the superior vestibular nucleus. Purkinje cells of zones 2 and 4 projected to the magnocellular and parvicellular parts of the medial vestibular nucleus, while some also innervated the lateral vestibular nucleus or nucleus prepositus hypoglossi. The climbing fiber inputs to Purkinje cells in zones 1 and 3 were derived from neurons in the ventrolateral outgrowth of the contralateral inferior olive, whereas those in zones 2 and 4 were derived from the contralateral caudal dorsal cap. Purkinje cells in zones 1 and 2, but not in zones 3 and 4, were positively labeled for heat-shock protein-25. The present study illustrates that Purkinje cells in the murine flocculus are organized in discrete zones with specific functions, specific input - output relations, and a specific histochemical signature.

Action Potentials↗
PubMed2026

Zone equalisation normalisation for improved alignment of epigenetic signal.

MOTIVATION: High-throughput genomic technologies have transformed our understanding of biological systems, yet direct comparison and visualisation of these complex datasets remains challenging. Existing normalisation methods often fail to align genomic signal across samples due to sensitivity to sequencing depth differences and localised high-signal artefacts, leading to inconsistent replicate behaviour and increased downstream variability. RESULTS: We introduce Zone Equalisation Normalisation (ZEN), a novel approach designed to improve cross-sample signal alignment of genomic data. ZEN rescales genomic signal based on variance estimated within biologically enriched regions, reducing the influence of extreme outliers while preserving underlying biological structure. Using a diverse collection of data and our new genome-wide benchmarking approach, we reveal that ZEN improves biological and technical replicate alignment across the majority of tested conditions and experimental platforms. We further show that this improved signal comparability is associated with fewer differential accessibility calls between technical replicates and a more conservative set of biological differences. Together, these results demonstrate that ZEN provides a complementary framework to improve the accuracy and reliability of genomic data analysis and that normalisation choice can affect downstream analyses and biological interpretation. AVAILABILITY AND IMPLEMENTATION: ZEN is available as an open-source Python package via conda and PyPI. Source code, documentation, tutorials, and code to reproduce the analyses are available at https://github.com/Genome-Function-Initiative-Oxford/Zone-Equalisation-Normalisation and Zenodo (https://doi.org/10.5281/zenodo.21067751).

Epigenesis, Genetic↗
PubMed2002

The complexities of interviewing Italo-Australian men about sensitive health issues.

The increase in the incidence of prostate cancer in Australia has been followed by an increase in prostate cancer awareness among Australian adults. However, men's level of knowledge on the subject has never been systematically assessed (Laws et al, 2000). It was postulated by Laws et al., (2000) that many men from Non English Speaking Cultures (NESC) experience language and cultural difficulties that would ultimately impinge on their ability to access information about prostate problems. In exploring 'The knowledge and attitudes of Italo-Australian men toward prostate cancer' the researchers became aware that the majority of interviewees (n=20) were reluctant to divulge information on all aspects of the topic (Drummond et al., 2001). This report highlights the importance of using a reflexive phase within the research process as a means of identifying factors that can, in part, explain the paucity of data and act a basis for developing strategies to overcome the problem. The research subsequently evolved to incorporate a secondary research question. 'Why were the men at interview so reluctant to speak of general health problems and health problems related to prostatic dysfunction?' A focus group comprised of Italo-Australian men was used to explore gender and culturalfactors, perceived by the researchers as, restricting theflow of information. Several barriers thought to be limiting the release of information were confirmed. We conclude that our findings will have implications for other researchers wanting to maximise their chances of accessing information rich datafrom the experiences of men from NESCs.

Australia↗
PubMed2003

Economic evaluation of specialist cancer and palliative nursing: Macmillan evaluation study findings.

Economic evaluation of specialist nursing interventions is challenging because of the complex nature of interventions and the difficulty of describing nursing outcomes in simple ways. This article discusses data from a study of Macmillan specialist cancer nursing. Resource-use data and nursing-outcome data were collated from 76 case studies of patients referred to 12 specialist cancer and palliative nursing teams (home-based and hospital-based) in the UK. Specific outcomes related to nursing were defined, and cost and nursing outcome data were analysed together. The data suggested that patients who reported better nursing outcomes had a higher proportion of specialist nursing interventions than those reporting poor nursing outcomes (45% versus 25%). Also, the overall pattern of health-care use was different for those patients who reported positive nursing outcomes. This suggests that positive nursing outcomes can influence patients' access to other health services. The data supported specific hypotheses regarding ways that specialist nurses can influence the cost-effectiveness of care. These data do not constitute a comparative evaluation study, as no control group was identified. Such results are nevertheless important as this type of data has not been gathered previously.

Cost Control↗
PubMed2003

IL-12 receptor deficiency revisited: IL-23-mediated signaling is also impaired in human genetic IL-12 receptor beta1 deficiency.

IFN-gamma and IL-12 are crucial cytokines for cell-mediated immunity against intracellular pathogens. We have previously shown that human IL-12Rbeta1-deficiency leads to impaired IL-12 responsiveness and unusual susceptibility to infections due to mycobacteria and salmonellae. IL-23 is a cytokine with functions that partially overlap with those of IL-12. IL-23 consists of IL-12p40 and a novel p19 protein, and binds to a receptor complex comprising IL-12Rbeta1 and IL-23R. Thus, IL-12Rbeta1-deficiency may impair both IL-12- and IL-23 signaling, and both may contribute to the immunological phenotypes. To examine whether IL-12Rbeta1 is essential for IL-23 signaling in human T cells, we have studied IL-23 responsiveness of four IL-12Rbeta1-deficient individuals. Whereas IL-23 promoted IFN-gamma production by CD4(+) and CD8(+) T cells in controls, IL-12Rbeta1-deficient T cells lacked IL-23-induced IFN-gamma secretion, but responded normally to IL-2, IL-4, IL-15 and IL-18. We also show that induction of IFN-gamma production by IL-23 depends upon TCR-ligation and is enhanced by CD28-costimulation. Furthermore, IL-23 cooperates with IL-12 and IL-18 in promoting IFN-gamma production in controls, but not in patients. We conclude that IL-12Rbeta1-deficiency impairs IL-12- and IL-23-dependent signaling in human T cells. The syndrome caused by IL-12Rbeta1-deficiency thus needs to be reinterpreted as resulting from defective IL-12-as well as IL-23-mediated immunity.

Humans↗
PubMed2006

Efficient restraints for protein-protein docking by comparison of observed amino acid substitution patterns with those predicted from local environment.

The discovery that the functions of most eukaryotic gene products are mediated through multi-protein complexes makes the prediction of protein interactions one of the most important current challenges in structural biology. Rigid-body docking methods can generate a large number of alternative candidates, but it is difficult to discriminate the near-native interactions from the large number of false positives. Many different scoring functions have been developed for this purpose, but in most cases, experimental and biological information is still required for accurate predictions. We explore here the use of evolutionary restraints in evaluating rigid-body docking geometries. In order to identify potential interface residues we identify functional residues based on the comparison of observed amino acid substitutions with those predicted from local environment. The interface residues identified by this method are correctly located in 85% of the cases. These predicted interface residues are used to define distance restraints that help to score rigid-body docking solutions. We have developed the pyDockRST software, which uses the percentage of satisfied distance restraints, together with the electrostatics and desolvation binding energy, to identify correct docking orientations. This methodology dramatically improves the docking results when compared to the use of energy criteria alone, and is able to find the correct orientation within the top 20 docking solutions in 80% of the cases.

Amino Acid Substitution↗
PubMed2005

Effect of B7-2 and CD40 signals from activated antigen-presenting cells on the ability of zwitterionic polysaccharides to induce T-Cell stimulation.

Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria elicit potent CD4+-T-cell responses in vivo and in vitro. We demonstrated that HLA-DR on professional antigen-presenting cells (APCs) is required for ZPS-induced T-cell proliferation in vitro (15). Recently, it was shown that ZPSs are processed to low-molecular-weight carbohydrates by a nitric oxide-mediated mechanism in endosomes and locate in the major histocompatibility complex class II pathway (5, 15). The effect of the ZPS-mediated expression of HLA-DR and costimulatory molecules on the APC and T-cell engagement and subsequent T-cell activation has not been elucidated. Herein, we report that ZPS-mediated induction of HLA-DR-surface expression and T-cell proliferation are maximally enhanced after incubation of APCs for 8 h with ZPS. Treatment of APCs with bafilomycin A inhibits the up-regulation of ZPS-mediated HLA-DR surface expression and leads to inhibition of T-cell proliferation. Monoclonal antibodies (MAbs) to the costimulatory molecules B7-2 and CD40L specifically block ZPS-mediated T-cell activation, while a MAb to B7-1 does not. Surface expression of B7-2 and B7-1 but not of CD40 is maximally enhanced at 8 to 16 h of treatment of APCs with ZPS. The results demonstrate that the cellular immune response to ZPS depends on the translocation of HLA-DR to the cell surface and requires costimulation via B7-2 and CD40 on activated APCs. The implication is that activation of ZPS-specific T cells requires an orchestrated arrangement of both presenting and costimulatory molecules to form an immunological synapse.

Antigen-Presenting Cells↗
PubMed2005

Human leukocyte antigen-DQ8 transgenic mice: a model to examine the toxicity of aerosolized staphylococcal enterotoxin B.

Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently emulate human responses to these toxins. Here, we report that human leukocyte antigen-DQ8 (HLA-DQ8) transgenic (Tg) mice, but not littermate controls, succumbed to lethal shock induced by SEB aerosols without potentiation. Substantial amounts of perivascular edema and inflammatory infiltrates were noted in the lungs of Tg mice, similar to the pathology observed in nonhuman primates exposed by aerosol to SEB. Furthermore, the observed pathologies and lethal shock correlated with an upsurge in proinflammatory cytokine mRNA gene expression in the lungs and spleens, as well as with marked increases in the levels of proinflammatory circulating cytokines in the Tg mice. Unlike the case for littermate controls, telemetric evaluation showed significant hypothermia in Tg mice exposed to lethal doses of SEB. Taken together, these results show that this murine model will allow for the examination of therapeutics and vaccines developed specifically against SEB aerosol exposure and possibly other bacterial superantigens in the context of human MHC class II receptors.

Aerosols↗
PubMed2006

What makes a champion? Explaining variation in human athletic performance.

Variation in human athletic performance is determined by a complex interaction of socio-cultural, psychological, and proximate physiological factors. Human physiological trait variance has both an environmental and genetic basis, although the classic gene-environment dichotomy is clearly too simplistic to understand the full range of variation for most proximate determinants of athletic performance, e.g., body composition. In other words, gene and environment interact, not just over the short term, but also over the lifetime of an individual with permanent effects on the adult phenotype. To further complicate matters, gene and environment may also be correlated. That is, genetically gifted individuals may be identified as children and begin training pulmonary, cardiovascular, and muscle systems at an early critical age. This review covers evidence in support of a genetic basis to human athletic performance, with some emphasis on the recent explosion of candidate gene studies. In addition, the review covers environmental influences on athletic performance with an emphasis on irreversible environmental effects, i.e., developmental effects that may accrue during critical periods of development either before conception (epigenetic effects), during fetal life (fetal programming), or during childhood and adolescence. Throughout, we emphasize the importance of gene-environment interaction (G x E) as a means of understanding variation in human physiological performance and we promote studies that integrate genomics with developmental biology.

Cardiovascular Physiological Phenomena↗
PubMed2003

Contrasting relatedness patterns in bottlenose dolphins (Tursiops sp.) with different alliance strategies.

Male bottlenose dolphins (Tursiops sp.) in Shark Bay have one of the most complex male societies outside humans. Two broad mating strategies have been identified in males. In the first strategy, there are two types of alliances: stable 'first-order' pairs and trios that herd individual females in reproductive condition, and 'second-order' teams of two first-order alliances (five or six individuals) that join forces against rivals in contests for females. In the alternative strategy, a 'super-alliance' of ca. 14 individuals, males form pairs or trios to herd females, but in contrast to the stable alliances, these pairs and trios are highly labile. Here, we show that males in stable first-order alliances and the derived second-order alliances are often strongly related, so that they may gain inclusive fitness benefits from alliance membership. By contrast, members of the super-alliance are no more closely related than expected by chance. Further, the strength of the association of alliance partners within the super-alliance, as measured by an index of joint participation in consorting a female, was not correlated with their genetic relatedness. Thus, within one population and one sex, it appears that there may be simultaneous operation of more than one mode of group formation.

Animals↗
PubMed2003

Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair.

BACKGROUND: Complement activation contributes to ischemia-reperfusion injury. Patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair suffer extensive ischemia-reperfusion and considerable systemic inflammation. METHODS AND RESULTS: The degree and mechanism of complement activation and its role in inflammation were investigated in 19 patients undergoing TAAA repair. Patients undergoing open infrarenal aortic surgery (n=5) or endovascular descending aortic aneurysm repair (n=6) served as control subjects. Substantial complement activation was seen in TAAA patients but not in controls. C1rs-C1-inhibitor complexes increased moderately, whereas C4bc, C3bBbP, C3bc, and the terminal SC5b-9 complex (TCC) increased markedly after reperfusion, reaching a maximum 8 hours after reperfusion. Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-8 increased significantly in TAAA patients but not in controls, peaking at 24 hours postoperatively and correlating closely with the degree of complement activation. IL-6 and IL-10 increased to a maximum 8 hours after reperfusion in the TAAA patients, were not correlated with complement activation, and increased moderately in the control subjects. Myeloperoxidase and lactoferrin increased markedly before reperfusion in all groups, whereas sICAM-1, sP-selectin, and sE-selectin were unchanged. No increase was observed in complement activation products, IL-1beta, TNF-alpha, or IL-8 in a mannose-binding lectin (MBL)-deficient TAAA patient, whereas IL-6, IL-10, myeloperoxidase, and lactoferrin increased as in the controls. Two other MBL-deficient TAAA patients receiving plasma attained significant MBL levels and showed complement and cytokine patterns identical to the MBL-sufficient TAAA patients. CONCLUSIONS: The data suggest that complement activation during TAAA repair is MBL mediated, amplified through the alternative pathway, and responsible in part for the inflammatory response.

Aged↗
PubMed2003

Complement activation in early protocol kidney graft biopsies after living-donor transplantation.

BACKGROUND: To gain insight into complement activation in kidney grafts, we studied the deposition of components from all complement pathways in protocol biopsies from living-donor recipients that were taken 1 week (median 7 days) after transplantation. METHODS: Graft protocol biopsies (n=37) were taken consecutively and stained for two-color immunofluorescence, with antibodies to C4d, C3, C1q, factor B, C6, terminal C5b-9 complement complex, mannose-binding lectin (MBL), and MBL-associated serine protease-1, combined with an endothelial marker. Light and electron microscopy were performed in all cases. Clinical acute rejection (AR), graft loss, and long-term kidney function were recorded. Baseline biopsies from 15 of the patients served as controls. RESULTS: Endothelial C4d deposition was demonstrated in peritubular capillaries in 11 of 37 cases (30%), of which 9 of 11 (82%) experienced clinical AR but only 6 of 11 (55%) experienced AR as defined by histopathologic criteria. Biopsies from three patients, two with early graft loss, showed diffuse global C4d in the glomerular endothelium with codeposition of C3 in all patients and MBL-associated serine protease-1 in one patient. Focal peritubular capillary C3 deposition was found in two additional C4d-positive cases with AR. No posttransplant deposition was demonstrated for the other components. CONCLUSIONS: Early diffuse C4d deposition in the kidney graft capillaries is closely related to acute humoral rejection, whereas focal staining may occur with mild AR or, rarely, without rejection. Codeposition of C3 indicates early AR with a higher risk of graft loss. In most cases, activation was limited to C4d, indicating efficient in situ regulation of complement activation.

Acute Disease↗
PubMed2006

Predicting the strongest domain-domain contact in interacting protein pairs.

Experiments to determine the complete 3-dimensional structures of protein complexes are difficult to perform and only a limited range of such structures are available. In contrast, large-scale screening experiments have identified thousands of pairwise interactions between proteins, but such experiments do not produce explicit structural information. In addition, the data produced by these high through-put experiments contain large numbers of false positive results, and can be biased against detection of certain types of interaction. Several methods exist that analyse such pairwise interaction data in terms of the constituent domains within proteins, scoring pairs of domain superfamilies according to their propensity to interact. These scores can be used to predict the strongest domain-domain contact (the contact with the largest surface area) between interacting proteins for which the domain-level structures of the individual proteins are known. We test this predictive approach on a set of pairwise protein interactions taken from the Protein Quaternary Structure (PQS) database for which the true domain-domain contacts are known.While the overall prediction success rate across the whole test data set is poor, we shown how interactions in the test data set for which the training data are not informative can be automatically excluded from the prediction process, giving improved prediction success rates at the expense of restricted coverage of the test data.

Binding Sites↗