RESUMEN
According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.
Asunto(s)
Internet , Pliegue de Proteína , Proteínas , Programas Informáticos , Proteínas/química , Termodinámica , Conformación Proteica , Evolución Molecular , Modelos MolecularesRESUMEN
SUMMARY: Once folded, natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i.e. they are highly frustrated. These regions, kept in place over evolutionary and physiological timescales, are related to several functional aspects of natural proteins such as protein-protein interactions, small ligand recognition, catalytic sites and allostery. Here, we present FrustratometeR, an R package that easily computes local energetic frustration on a personal computer or a cluster. This package facilitates large scale analysis of local frustration, point mutants and molecular dynamics (MD) trajectories, allowing straightforward integration of local frustration analysis into pipelines for protein structural analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/proteinphysiologylab/frustratometeR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Asunto(s)
Simulación de Dinámica Molecular , Proteínas , Dominio Catalítico , Programas InformáticosRESUMEN
Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
Asunto(s)
Enzimas/química , Modelos Moleculares , Pliegue de Proteína , Dominio CatalíticoRESUMEN
Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.
Asunto(s)
Enfermedades de von Willebrand/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Advances in single-cell transcriptomics techniques are revolutionizing studies of cellular differentiation and heterogeneity. It has become possible to track the trajectory of thousands of genes across the cellular lineage trees that represent the temporal emergence of cell types during dynamic processes. However, reconstruction of cellular lineage trees with more than a few cell fates has proved challenging. We present MERLoT (https://github.com/soedinglab/merlot), a flexible and user-friendly tool to reconstruct complex lineage trees from single-cell transcriptomics data. It can impute temporal gene expression profiles along the reconstructed tree. We show MERLoT's capabilities on various real cases and hundreds of simulated datasets.
Asunto(s)
Diferenciación Celular/genética , Linaje de la Célula/genética , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Programas Informáticos , Algoritmos , Animales , Análisis por Conglomerados , Células Madre Hematopoyéticas/metabolismo , Humanos , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Factores de Tiempo , Transcriptoma/genéticaRESUMEN
SUMMARY: Cellular lineage trees can be derived from single-cell RNA sequencing snapshots of differentiating cells. Currently, only datasets with simple topologies are available. To test and further develop tools for lineage tree reconstruction, we need test datasets with known complex topologies. PROSSTT can simulate scRNA-seq datasets for differentiation processes with lineage trees of any desired complexity, noise level, noise model and size. PROSSTT also provides scripts to quantify the quality of predicted lineage trees. AVAILABILITY AND IMPLEMENTATION: https://github.com/soedinglab/prosstt. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Asunto(s)
Programas Informáticos , Diferenciación Celular , Perfilación de la Expresión Génica , RNA-Seq , Análisis de la Célula IndividualRESUMEN
BACKGROUND: Oncoplastic surgery (OPS) allows wider resections with immediate breast reshaping by mammoplasty. This study reviews our experience with level 2 mammoplasties in patients with histology-proven pure ductal carcinoma in situ (DCIS). METHOD: From a prospectively maintained database of 392 consecutive oncoplastic level 2 mammoplasties, 68 patients presented with pure DCIS. Involved margin rates and locoregional recurrence rates were calculated, with 76 months (0-166 months) median follow-up. RESULTS: The mean pathological tumor size was 34 mm (median 26 mm, range 2-106 mm). The mean resection weight was 191 g (median 131 g, range 40-1150 g). Margins were clear in 58 cases (85.3%) and involved in 10 cases (14.7%). Margins were involved in 1 out of 54 (1.9%) cases with tumor size under 50 mm and in 9 out of 14 (64.3%) cases with tumor size higher than 50 mm (p < 0.001). On multivariable analysis, only tumor size > 50 mm [odds ratio (OR) 95.400; p < 0.001] was independently associated with involved margins. Seven patients had mastectomy. The overall breast conservation rate was 89.4%, and 100% for tumors less than 5 cm. There were three local recurrences. The 5-year cumulative incidence for local recurrence was 5.5% (0-11.5%). CONCLUSIONS: OPS is a safe solution for large DCIS up to 50 mm, with an involved margin rate of only 1.9%, and can thus reduce the mastectomy rate in this group. As margin involvement significantly increases for tumors larger than 5 cm, better preoperative localization and/or wider excisions are necessary in this group.
Asunto(s)
Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Mamoplastia/métodos , Márgenes de Escisión , Mastectomía/métodos , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
This article describes the motivation, origin and evolution of the student symposia series organised by the ISCB Student Council. The meeting series started thirteen years ago in Madrid and has spread to four continents. The article concludes with the highlights of the most recent edition of annual Student Council Symposium held in conjunction with the 25th Conference on Intelligent Systems for Molecular Biology and the 16th European Conference on Computational Biology, in Prague, in July 2017.
Asunto(s)
Biología Computacional , Congresos como Asunto , Estudiantes , Becas , Humanos , Revisión de la Investigación por Pares , Publicaciones , Apoyo a la Investigación como Asunto/economíaRESUMEN
BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Ductal de Mama/tratamiento farmacológico , Tratamiento Conservador/métodos , Estadificación de Neoplasias , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Carcinoma Ductal de Mama/patología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
OBJECTIVES: Patients with severe haemophilia A (HA) receive factor VIII (FVIII) replacement therapy as prophylaxis. myPKFiT® is an online medical application that allows authorized users to simulate dosing regimens with patient pharmacokinetic (PK) profiles based on only 2 blood samples. Our aim was to assess the impact of using this medical device in routine practice in terms of FVIII consumption and clinical outcomes. METHODS: Thirty-six patients with severe HA on prophylaxis with Advate® were recruited in 3 centres in Spain. Annual bleeding rate (ABR), annual joint bleeding rate (AJBR) and annual FVIII consumption before and after adjustment were obtained using the patient's clinical history (12 months before) and prospectively recorded data (12 months after), respectively. Adjustment was based on PK parameters provided by myPKFiT® , joint status and relative risk associated with physical activity and bleeding phenotype. RESULTS: ABR and AJBR were significantly reduced after adjustment in the overall sample (-2.2 ± 1.3, P = .018 and -1.9 ± 1.2, P = .012, respectively) and in patients aged >15 years (-2.6 ± 1.4, P = .011 and -2.0 ± 1.2, P = .005, respectively). Adjustment had an effect on the individual FVIII consumption of most patients: annual amount was reduced in 18 cases and increased in 14. There was no significant effect on the mean amount (198 784 ± 110 387) compared to that used the year prior to myPKFiT® -adjusted prophylaxis (199 466 ± 103 670; P = .737). DISCUSSION: Our results suggest that PK-guided prophylaxis using myPKFiT® improved clinical outcomes and optimized FVIII consumption in the study population. This personalized approach may reduce bleeding rates without significantly increasing the overall cost of FVIII therapy.
Asunto(s)
Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Adolescente , Adulto , Teorema de Bayes , Niño , Factor VIII/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Outcome data on treatment of patients with haemophilia A spanning several years of real-world evidence collection are currently very limited. AIM AND METHODS: The global prospective long-term Advate® Haemophilia A Outcome Database (AHEAD) cohort study collects real-world data from patients with severe and moderate haemophilia. We report an interim data read-out after three years of observation. RESULTS: A total of 522 patients were enrolled from 21 countries: 334 completed year 1 follow-up, 238 completed year 2 and 136 completed year 3, with an overall follow-up of 811 patient-years. Median annual bleeding rates (ABR) were 1.7 in the prophylaxis group and 8.9 in the on-demand group at year 1 visit, 1.6 and 13.0, respectively, at year 2 visit and 2.2 and 10.3, respectively, at year 3 visit. Moreover, about 42% of patients on prophylaxis vs 12% of patients on on-demand had zero annual joint bleeding rates (AJBR). Effectiveness of prophylaxis and on-demand treatment was deemed excellent/good in the majority of cases. Octocog alfa (Advate® ) was well tolerated. The inhibitors that developed in nine patients all disappeared spontaneously. Three patients had been previously exposed to FVIII for ≤50 exposure days (EDs), 3 for >50 EDs and 3 showed a borderline positive inhibitory activity (≤0.6 BU/mL). CONCLUSIONS: These data confirm that the goal of zero bleeds is achievable, although not yet achieved in all patients. Understanding reasons behind the lower response to standard prophylaxis regimens in some patients and personalizing prophylactic treatment may further improve outcome in patients with haemophilia A.
Asunto(s)
Factor VIII/uso terapéutico , Hemofilia A/patología , Hemorragia/prevención & control , Adolescente , Adulto , Anciano , Inhibidores de Factor de Coagulación Sanguínea/sangre , Niño , Preescolar , Bases de Datos Factuales , Factor VIII/efectos adversos , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Artropatías/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing covariations in extant sequences. Still, many natural proteins that fold into the same structural topology show different stabilization energies, and these are often related to their physiological behavior. We propose a description for the energetic variation given by sequence modifications in repeat proteins, systems for which the overall problem is simplified by their inherent symmetry. We explicitly account for single amino acid and pair-wise interactions and treat higher order correlations with a single term. We show that the resulting evolutionary field can be interpreted with structural detail. We trace the variations in the energetic scores of natural proteins and relate them to their experimental characterization. The resulting energetic evolutionary field allows the prediction of the folding free energy change for several mutants, and can be used to generate synthetic sequences that are statistically indistinguishable from the natural counterparts.
Asunto(s)
Evolución Química , Modelos Moleculares , Proteínas/química , Proteínas/ultraestructura , Secuencias Repetitivas de Aminoácido/genética , Análisis de Secuencia de Proteína/métodos , Transferencia de Energía , Modelos Químicos , Mutación Puntual/genética , Conformación Proteica , Pliegue de Proteína , Proteínas/genética , Relación Estructura-ActividadRESUMEN
The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar.
Asunto(s)
Algoritmos , Proteínas Nucleares/química , Ácidos Nucleicos/química , Nucleosomas/química , Interfaz Usuario-Computador , Secuencia de Aminoácidos , Gráficos por Computador , Humanos , Internet , Simulación de Dinámica Molecular , Proteínas Nucleares/genética , Ácidos Nucleicos/genética , Nucleosomas/genética , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , Análisis de Secuencia de Proteína , Electricidad Estática , TermodinámicaRESUMEN
INTRODUCTION: Tetralogy of Fallot (TOF) is the most frequent cyanotic congenital heart disease. Pulmonary regurgitation (PR) and right ventricle (RV) enlargement and dysfunction are the most common long-term complications. Cardiac magnetic resonance (CMR) is the gold standard for RV evaluation. OBJECTIVE: To analyze CMR results in the follow-up of TOF patients. PATIENTS AND METHOD: All CMR performed between 2007 and 2012 in TOF patients with transannular patch (TAP) repair or infundibular widening, and without pulmonary valve replacement (PVR) were included. Pulmonary regurgitant fraction (PRF), ventricular end-diastolic (EDV) and end-systolic volume (ESV), and ejection fraction (EF) were examined. RESULTS: 122 CMR were performed in 114 patients. Average age at CMR was 15.4±7.4 years. 53.3% of them presented severe PR (> 40%). RVEDV was 157.3 ± 38.6 ml/m2, RVESV was 85.3 ± 27 ml/m2 and RVEF was 46.4 ± 7.1%. RVEDV was > 150 ml/ m2 in 48.4% and > 170 ml/m2 in 32.8% of patients. Patients with TAP showed larger RV volumes compared with those with infundibular widening. RVEDV > 170 ml/m2 showed worse RVEF that those with lower RVEDV (47.9 ± 7% vs 43.2 ± 6.4%, p < 0.01). CONCLUSION: Almost half of the pa tients showed significant RV enlargement, demonstrating that the indication of CMR is late in their follow-up. TAP was associated with higher RVEDV and RVESV, but no worse RVEF.
Asunto(s)
Hipertrofia Ventricular Derecha/diagnóstico por imagen , Imagen por Resonancia Magnética , Complicaciones Posoperatorias/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Disfunción Ventricular Derecha/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Hipertrofia Ventricular Derecha/etiología , Lactante , Masculino , Estudios Retrospectivos , Tetralogía de Fallot/diagnóstico por imagen , Disfunción Ventricular Derecha/etiologíaRESUMEN
UNLABELLED: INSECT is a user-friendly web server to predict the occurrence of Cis-Regulatory Modules (CRMs), which control gene expression. Here, we present a new release of INSECT which includes several new features, such as whole genome analysis, nucleosome occupancy predictions, and which provides additional links to third-party functional tools that complement user capabilities, CRM analysis and hypothesis construction. Improvements in the core implementation have led to a faster and more efficient tool. In addition, this new release introduces a new interface designed for a more integrative and dynamic user experience. AVAILABILITY AND IMPLEMENTATION: http://bioinformatics.ibioba-mpsp-conicet.gov.ar/INSECT2 CONTACT: pyankilevich@ibioba-mpsp-conicet.gov.ar.
Asunto(s)
Simulación por Computador , Genoma , Factores de Transcripción , Algoritmos , Sitios de Unión , Internet , Elementos Reguladores de la TranscripciónRESUMEN
BACKGROUND: Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development. METHODS: We used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch). RESULTS: We identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5-135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases. CONCLUSIONS: By studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs.
Asunto(s)
Historia Natural/métodos , Adulto , Hemofilia A/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIM: This observational study was undertaken with the aim to describe the characteristics and evaluate the outcomes of prophylactic treatment in children with severe haemophilia A (HA) treated at our centre. METHODS: Twenty-five patients aged 4-19 years with severe HA, no history of inhibitors and treated with at least two infusions of factor VIII (FVIII) per week were studied. Prophylactic doses and annual joint bleeding rate (AJBR) were retrospectively evaluated over the last 5 years. Current joint status was assessed using the Haemophilia Joint Health Score (HJHS) (136 joints of 23 patients) and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) procedure (124 joints of 21 patients). RESULTS: Median AJBR was 0.2 and median prophylaxis dose 65.4 IU-1 kg-1 week-1 . Median total HJHS was 0 (range 0-13) and total HEAD-US 1 (0-8). At the joint level, 85.3% of joints were normal on HJHS and 79.0% on US. The ankle was the joint most commonly affected, considering bleeding and ultrasound results. Correlation was found between HEAD-US scores and bleeding scores but not between HEAD-US and HJHS scores. HJHS and HEAD-US scores were concordant in 91/124 (73.4%) joints (86 joints normal and five abnormal). Ultrasound detected minimal changes in 19.6% of joints with normal physical function, whereas 12.2% of joints considered normal on ultrasound showed changes at HJHS. CONCLUSION: A well-preserved joint status was found in our cohort. High-resolution US detected a higher percentage of abnormalities than the physical evaluation, but the clinical implications of these findings still need to be ascertained.
RESUMEN
Ankyrin repeat containing proteins are one of the most abundant solenoid folds. Usually implicated in specific protein-protein interactions, these proteins are readily amenable for design, with promising biotechnological and biomedical applications. Studying repeat protein families presents technical challenges due to the high sequence divergence among the repeating units. We developed and applied a systematic method to consistently identify and annotate the structural repetitions over the members of the complete Ankyrin Repeat Protein Family, with increased sensitivity over previous studies. We statistically characterized the number of repeats, the folding of the repeat-arrays, their structural variations, insertions and deletions. An energetic analysis of the local frustration patterns reveal the basic features underlying fold stability and its relation to the functional binding regions. We found a strong linear correlation between the conservation of the energetic features in the repeat arrays and their sequence variations, and discuss new insights into the organization and function of these ubiquitous proteins.
Asunto(s)
Repetición de Anquirina , Ancirinas/química , Ancirinas/ultraestructura , Modelos Químicos , Modelos Moleculares , Secuencia de Aminoácidos , Simulación por Computador , Transferencia de Energía , Datos de Secuencia Molecular , Análisis de Secuencia de Proteína/métodosAsunto(s)
Tejido Adiposo/trasplante , Amiloidosis Familiar/etiología , Técnicas Cosméticas/efectos adversos , Enfermedades Cutáneas Genéticas/etiología , Amiloidosis Familiar/patología , Autoinjertos , Femenino , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Enfermedades Cutáneas Genéticas/patologíaRESUMEN
RepeatsDB (http://repeatsdb.bio.unipd.it/) is a database of annotated tandem repeat protein structures. Tandem repeats pose a difficult problem for the analysis of protein structures, as the underlying sequence can be highly degenerate. Several repeat types haven been studied over the years, but their annotation was done in a case-by-case basis, thus making large-scale analysis difficult. We developed RepeatsDB to fill this gap. Using state-of-the-art repeat detection methods and manual curation, we systematically annotated the Protein Data Bank, predicting 10,745 repeat structures. In all, 2797 structures were classified according to a recently proposed classification schema, which was expanded to accommodate new findings. In addition, detailed annotations were performed in a subset of 321 proteins. These annotations feature information on start and end positions for the repeat regions and units. RepeatsDB is an ongoing effort to systematically classify and annotate structural protein repeats in a consistent way. It provides users with the possibility to access and download high-quality datasets either interactively or programmatically through web services.