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B Rost

Publications and source records attributed to B Rost.

At least 19 recordsLinked to original sources
PubMed2004

Annotating proteins from endoplasmic reticulum and Golgi apparatus in eukaryotic proteomes.

The sub-cellular localization of a native protein constitutes one coarse-grained aspect of its function. Transport between compartments is often regulated through short sequence motifs. Here, we analyzed experimentally characterized endoplasmic reticulum (ER)/ Golgi retrieval motifs and investigated the accuracy of homology-transfer. Only the C-terminal ER retrieval motifs KDEL, HDEL and AIAKE were sufficiently specific. However, even unspecific motifs may help, provided we know the probability for localization given the motif. We provided such estimates. We also rigorously estimated the accuracy and coverage for inferring ER and Golgi localization through homology-transfer by sequence similarity. In entire proteomes, we could thereby annotate 3304 ER (3182 membrane) and 1853 Golgi (759 membrane) proteins. We identified another putative 5157 globular and 3941 membrane ER or Golgi proteins. Each experimental annotation yielded, on average, one to three high-accuracy and five to six low-accuracy homology-transfers in the six proteomes. These numbers will increase with each new experimental annotation.

Amino Acid Motifs↗
PubMed2003

Automatic prediction of protein function.

Most methods annotating protein function utilise sequence homology to proteins of experimentally known function. Such a homology-based annotation transfer is problematic and limited in scope. Therefore, computational biologists have begun to develop ab initio methods that predict aspects of function, including subcellular localization, post-translational modifications, functional type and protein-protein interactions. For the first two cases, the most accurate approaches rely on identifying short signalling motifs, while the most general methods utilise tools of artificial intelligence. An outstanding new method predicts classes of cellular function directly from sequence. Similarly, promising methods have been developed predicting protein-protein interaction partners at acceptable levels of accuracy for some pairs in entire proteomes. No matter how difficult the task, successes over the last few years have clearly paved the way for ab initio prediction of protein function.

Computational Biology↗
PubMed2002

[Value of contrast-enhanced ultrasound vs. CT and MRI in palpable enlarged lymph nodes of the head and neck].

PURPOSE: To compare the value of B-mode-, plain and contrast enhanced color Doppler ultrasound, CT and MRI with respect to their diagnostic accuracy in palpable enlarged cervical lymph nodes. MATERIAL AND METHODS: Thirty patients (18 - 90 years old) with palpable enlarged lymph nodes of the head and neck underwent B-mode-ultrasound, plain and contrast enhanced color Doppler, CT and MRI (gold standard: histologic analysis in 22 and clinical follow up for at least six months in eight patients). The criteria of malignancy were maximal and minimal lymph node diameter, M/Q-ratio, various morphologic criteria (necrosis, hilus line, internal structure, contour, contrast enhancement), spectral Doppler indices, and vascular architecture in color Doppler. RESULTS: The highest sensitivity (= 1.00, specificity = 0.07 - 0.15) was obtained measuring the lymph node diameter independent on the used imaging modality (ultrasound, CT, MRI), the highest specificity (= 1.00, sensitivity = 0.71) analyzing the vascularity of the lymph node by plain color Doppler. The highest diagnostic (= 0.93) accuracy was delivered by contrast enhanced color Doppler analysis of the vascularity. Sensitivity (= 0.94) and specificity (= 0.92) of this imaging modality were only slightly inferior to the top values. Fisher's exact test revealed significant values in differentiating malignant from benign lymph nodes for B-mode- and MR-analysis of the M/Q-ratio (p < 0001/p < 0.05), B-mode morphology (p < 0.00005), plain and contrast enhanced color Doppler analysis of the vascularity (p < 0.0001/p < 0.000005), MR-morphology (p < 0.0001), and CT-morphology (p < 0.005). CONCLUSION: CT is inferior to MRI, B-mode-ultrasound and contrast-enhanced color Doppler in the differential diagnosis of selectively analyzed, palpably enlarged cervical lymph nodes using the criteria of our study. The analysis of the MR-morphology revealed a slightly inferior diagnostic accuracy to B-mode morphology and color Doppler analysis of the vascularity.

Adolescent↗
PubMed2001

CAFASP2: the second critical assessment of fully automated structure prediction methods.

The results of the second Critical Assessment of Fully Automated Structure Prediction (CAFASP2) are presented. The goals of CAFASP are to (i) assess the performance of fully automatic web servers for structure prediction, by using the same blind prediction targets as those used at CASP4, (ii) inform the community of users about the capabilities of the servers, (iii) allow human groups participating in CASP to use and analyze the results of the servers while preparing their nonautomated predictions for CASP, and (iv) compare the performance of the automated servers to that of the human-expert groups of CASP. More than 30 servers from around the world participated in CAFASP2, covering all categories of structure prediction. The category with the largest participation was fold recognition, where 24 CAFASP servers filed predictions along with 103 other CASP human groups. The CAFASP evaluation indicated that it is difficult to establish an exact ranking of the servers because the number of prediction targets was relatively small and the differences among many servers were also small. However, roughly a group of five "best" fold recognition servers could be identified. The CASP evaluation identified the same group of top servers albeit with a slightly different relative order. Both evaluations ranked a semiautomated method named CAFASP-CONSENSUS, that filed predictions using the CAFASP results of the servers, above any of the individual servers. Although the predictions of the CAFASP servers were available to human CASP predictors before the CASP submission deadline, the CASP assessment identified only 11 human groups that performed better than the best server. Furthermore, about one fourth of the top 30 performing groups corresponded to automated servers. At least half of the top 11 groups corresponded to human groups that also had a server in CAFASP or to human groups that used the CAFASP results to prepare their predictions. In particular, the CAFASP-CONSENSUS group was ranked 7. This shows that the automated predictions of the servers can be very helpful to human predictors. We conclude that as servers continue to improve, they will become increasingly important in any prediction process, especially when dealing with genome-scale prediction tasks. We expect that in the near future, the performance difference between humans and machines will continue to narrow and that fully automated structure prediction will become an effective companion and complement to experimental structural genomics.

Automation↗
PubMed2001

EVA: large-scale analysis of secondary structure prediction.

EVA is a web-based server that evaluates automatic structure prediction servers continuously and objectively. Since June 2000, EVA collected more than 20,000 secondary structure predictions. The EVA sets sufficed to conclude that the field of secondary structure prediction has advanced again. Accuracy increased substantially in the 1990s through using evolutionary information taken from the divergence of proteins in the same structural family. Recently, the evolutionary information resulting from improved searches and larger databases has again boosted prediction accuracy by more than 4% to its current height around 76% of all residues predicted correctly in one of the three states: helix, strand, or other. The best current methods solved most of the problems raised at earlier CASP meetings: All good methods now get segments right and perform well on strands. Is the recent increase in accuracy significant enough to make predictions even more useful? We believe the answer is affirmative. What is the limit of prediction accuracy? We shall see. All data are available through the EVA web site at [cubic.bioc.columbia.edu/eva/]. The raw data for the results presented are available at [eva]/sec/bup_common/2001_02_22/.

Databases, Protein↗
PubMed2001

Redox dependent conformational changes in the mixed valence form of the cytochrome c oxidase from p. The reorganization of glutamic acid 278 is coupled to the electron transfer from/to heme a and the binuclear center. denitrificans.

In this work we present the separation of FTIR difference signals induced by electron transfer to/from the redox centers of the cytochrome c oxidase from P. denitrificans and compare electrochemically induced FTIR difference spectra with those induced by CO photolysis. FTIR difference spectra of rebinding of CO to the half reduced (mixed valence) form of the cytochrome c oxidase after photolysis reflect the conformational changes induced by the rebinding of CO and by electron transfer reactions from heme a3 to heme a and further on to CUA. During this process, heme a3 (and CUB) are oxidized, whereas heme a and CuA are reduced. By subtracting these difference spectra from an electrochemically induced FTIR difference spectrum, where all four cofactors are reduced, the contributions for heme a3 (and CuB) could be separated. Correspondingly, the spectral contributions of heme a and CuA have been separated. The comparison of these spectra with the spectra calculated for the hemes on the basis of their redox dependent changes previously published in Hellwig et al., (Biochemistry 38, (1999) 1685-1694) show a high degree of similarity, except for additional signals coupled to the reorganization of the binuclear center upon CO rebinding. The separated spectra clearly show that the signals attributed to Glu278, an amino acid discussed to be crucial for proton pumping, is coupled to electron transfer to/from heme a and the binuclear heme a3-CuB center.

Electron Transport↗
PubMed2001

Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.

OBJECTIVE: To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls. DESIGN: A randomized controlled 3-month intervention trial, with an additional 3-month follow-up. SETTING: Out-patient geriatric rehabilitation unit. PARTICIPANTS: Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture. INTERVENTION: Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded. MEASUREMENTS: Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3). RESULTS: No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3-month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245). CONCLUSIONS: Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls.

Accidental Falls↗
PubMed2001

EVA: continuous automatic evaluation of protein structure prediction servers.

UNLABELLED: Evaluation of protein structure prediction methods is difficult and time-consuming. Here, we describe EVA, a web server for assessing protein structure prediction methods, in an automated, continuous and large-scale fashion. Currently, EVA evaluates the performance of a variety of prediction methods available through the internet. Every week, the sequences of the latest experimentally determined protein structures are sent to prediction servers, results are collected, performance is evaluated, and a summary is published on the web. EVA has so far collected data for more than 3000 protein chains. These results may provide valuable insight to both developers and users of prediction methods. AVAILABILITY: http://cubic.bioc.columbia.edu/eva. CONTACT: eva@cubic.bioc.columbia.edu

Automation↗
PubMed2001

Comparing function and structure between entire proteomes.

More than 30 organisms have been sequenced entirely. Here, we applied a variety of simple bioinformatics tools to analyze 29 proteomes for representatives from all three kingdoms: eukaryotes, prokaryotes, and archaebacteria. We confirmed that eukaryotes have relatively more long proteins than prokaryotes and archaes, and that the overall amino acid composition is similar among the three. We predicted that approximately 15%-30% of all proteins contained transmembrane helices. We could not find a correlation between the content of membrane proteins and the complexity of the organism. In particular, we did not find significantly higher percentages of helical membrane proteins in eukaryotes than in prokaryotes or archae. However, we found more proteins with seven transmembrane helices in eukaryotes and more with six and 12 transmembrane helices in prokaryotes. We found twice as many coiled-coil proteins in eukaryotes (10%) as in prokaryotes and archaes (4%-5%), and we predicted approximately 15%-25% of all proteins to be secreted by most eukaryotes and prokaryotes. Every tenth protein had no known homolog in current databases, and 30%-40% of the proteins fell into structural families with >100 members. A classification by cellular function verified that eukaryotes have a higher proportion of proteins for communication with the environment. Finally, we found at least one homolog of experimentally known structure for approximately 20%-45% of all proteins; the regions with structural homology covered 20%-30% of all residues. These numbers may or may not suggest that there are 1200-2600 folds in the universe of protein structures. All predictions are available at http://cubic.bioc.columbia.edu/genomes.

Amino Acids↗
PubMed2000

Reduced calcification of marine plankton in response to increased atmospheric CO2.

The formation of calcareous skeletons by marine planktonic organisms and their subsequent sinking to depth generates a continuous rain of calcium carbonate to the deep ocean and underlying sediments. This is important in regulating marine carbon cycling and ocean-atmosphere CO2 exchange. The present rise in atmospheric CO2 levels causes significant changes in surface ocean pH and carbonate chemistry. Such changes have been shown to slow down calcification in corals and coralline macroalgae, but the majority of marine calcification occurs in planktonic organisms. Here we report reduced calcite production at increased CO2 concentrations in monospecific cultures of two dominant marine calcifying phytoplankton species, the coccolithophorids Emiliania huxleyi and Gephyrocapsa oceanica. This was accompanied by an increased proportion of malformed coccoliths and incomplete coccospheres. Diminished calcification led to a reduction in the ratio of calcite precipitation to organic matter production. Similar results were obtained in incubations of natural plankton assemblages from the north Pacific ocean when exposed to experimentally elevated CO2 levels. We suggest that the progressive increase in atmospheric CO2 concentrations may therefore slow down the production of calcium carbonate in the surface ocean. As the process of calcification releases CO2 to the atmosphere, the response observed here could potentially act as a negative feedback on atmospheric CO2 levels.

Atmosphere↗
PubMed2000

Cutaneous manifestations in anorexia nervosa.

Anorexia nervosa is an eating disorder among adolescent girls and young women which, though common, often goes undetected and untreated. Anorexia nervosa is a response for young people with psychological conflicts who try to win love by having a body corresponding to the present-day image, symbolising strength, beauty, attraction, power and success. Anorexia nervosa involves inadequate calorie intake leading to marked cachexia with metabolic and endocrinological disturbances. We investigated dermatological changes in 21 young female anorectics aged 19-24 in an attempt to find dermatological markers which mirror the dynamics of the disease and thus obtain helpful signs for early diagnosis with its important bearing on the outcome. Extensive histories were taken and whole-body examinations performed. Seven sex- and age-matched persons served as a control group. The most common dermatological findings were xerosis (71%, controls 29%), cheilitis (76%), bodily hypertrichosis (62%), alopecia (24%), dry scalp hair (48%), acral coldness (38%), acrocyanosis (33%), periungual erythema (48%), gingival changes (37%), nail changes (29%) and calluses on dorsum of hand due to self-induced vomiting (67%). Our study documented for the first time that a body mass index of < or = 16 (kg/m2) can be considered a critical value at which skin changes are more frequent. There are remarkable similarities between cutaneous manifestations in anorexia nervosa and in HIV infection. Patients with anorexia nervosa develop early stereotype skin changes which are cardinal diagnostic symptoms and pointers to the diagnosis of eating disorders. During training at the Department of Child and Adolescent Psychiatry in Solothurn one of us (C. H.) was once more able to observe most of the above-described cutaneous and mucocutaneous changes in anorexic adolescents. This paper is intended to stimulate further basic research on this topic. We hope our study will facilitate early diagnosis of anorexia nervosa by the family physician and enable him or her to institute immediate treatment for the eating disorder and thereby improve the prognosis.

Adolescent↗
PubMed2000

Finding nuclear localization signals.

A variety of nuclear localization signals (NLSs) are experimentally known although only one motif was available for database searches through PROSITE. We initially collected a set of 91 experimentally verified NLSs from the literature. Through iterated 'in silico mutagenesis' we then extended the set to 214 potential NLSs. This final set matched in 43% of all known nuclear proteins and in no known non-nuclear protein. We estimated that >17% of all eukaryotic proteins may be imported into the nucleus. Finally, we found an overlap between the NLS and DNA-binding region for 90% of the proteins for which both the NLS and DNA-binding regions were known. Thus, evolution seemed to have used part of the existing DNA-binding mechanism when compartmentalizing DNA-binding proteins into the nucleus. However, only 56 of our 214 NLS motifs overlapped with DNA-binding regions. These 56 NLSs enabled a de novo prediction of partial DNA-binding regions for approximately 800 proteins in human, fly, worm and yeast.

Animals↗
PubMed1999

Effective use of sequence correlation and conservation in fold recognition.

Protein families are a rich source of information; sequence conservation and sequence correlation are two of the main properties that can be derived from the analysis of multiple sequence alignments. Sequence conservation is related to the direct evolutionary pressure to retain the chemical characteristics of some positions in order to maintain a given function. Sequence correlation is attributed to the small sequence adjustments needed to maintain protein stability against constant mutational drift. Here, we showed that sequence conservation and correlation were each frequently informative enough to detect incorrectly folded proteins. Furthermore, combining conservation, correlation, and polarity, we achieved an almost perfect discrimination between native and incorrectly folded proteins. Thus, we made use of this information for threading by evaluating the models suggested by a threading method according to the degree of proximity of the corresponding correlated, conserved, and apolar residues. The results showed that the fold recognition capacity of a given threading approach could be improved almost fourfold by selecting the alignments that score best under the three different sequence-based approaches.

Amino Acid Sequence↗
PubMed1999

Time-resolved FT-IR studies on the CO adduct of Paracoccus denitrificans cytochrome c oxidase: comparison of the fully reduced and the mixed valence form.

The rebinding of CO to cytochrome c oxidase from Paracoccus denitrificans in the fully reduced and in the half-reduced (mixed valence) form as a function of temperature was investigated using time-resolved rapid-scan FT-IR spectroscopy in the mid-IR (1200-2100 cm-1). For the fully reduced enzyme, rebinding was complete in approximately 2 s at 268 K and showed a biphasic reaction. At 84 K, nonreversible transfer of CO from heme a3 to CuB was observed. Both photolysis at 84 K and photolysis at 268 K result in FT-IR difference spectra which show similarities in the amide I, amide II, and heme modes. Both processes, however, differ in spectral features characteristic for amino acid side chain modes and may thus be indicative for the motional constraint of CO at low temperature. Rebinding of photodissociated CO for the mixed-valence enzyme at 268 K is also biphasic, but much slower as compared to the fully reduced enzyme. FT-IR difference spectra show band features similar to those for the fully reduced enzyme. Additional strong bands in the amide I and amide II range indicate local conformational changes induced by electron and coupled proton transfer. These signals disappear when the temperature is lowered to 84 K. At 268 K, a difference signal at 1746 cm-1 is observed which is shifted by 6 cm-1 to 1740 cm-1 in 2H2O. The absence of this signal for the mutant Glu 278 Gln allows assignment to the COOH stretching mode of Glu 278, and indicates changes of the conformation, proton position, or protonation of this residue upon electron transfer.

Carbon Monoxide↗
PubMed1999

A modified definition of Sov, a segment-based measure for protein secondary structure prediction assessment.

We present a measure for the evaluation of secondary structure prediction methods that is based on secondary structure segments rather than individual residues. The algorithm is an extension of the segment overlap measure Sov, originally defined by Rost et al. (J Mol Biol 1994;235:13-26). The new definition of Sov corrects the normalization procedure and improves Sov's ability to discriminate between similar and dissimilar segment distributions. The method has been comprehensively tested during the second Critical Assessment of Techniques for Protein Structure Prediction (CASP2). Here, we describe the underlying concepts, modifications to the original definition, and their significance.

Algorithms↗
PubMed1999

CAFASP-1: critical assessment of fully automated structure prediction methods.

The results of the first Critical Assessment of Fully Automated Structure Prediction (CAFASP-1) are presented. The objective was to evaluate the success rates of fully automatic web servers for fold recognition which are available to the community. This study was based on the targets used in the third meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP-3). However, unlike CASP-3, the study was not a blind trial, as it was held after the structures of the targets were known. The aim was to assess the performance of methods without the user intervention that several groups used in their CASP-3 submissions. Although it is clear that "human plus machine" predictions are superior to automated ones, this CAFASP-1 experiment is extremely valuable for users of our methods; it provides an indication of the performance of the methods alone, and not of the "human plus machine" performance assessed in CASP. This information may aid users in choosing which programs they wish to use and in evaluating the reliability of the programs when applied to their specific prediction targets. In addition, evaluation of fully automated methods is particularly important to assess their applicability at genomic scales. For each target, groups submitted the top-ranking folds generated from their servers. In CAFASP-1 we concentrated on fold-recognition web servers only and evaluated only recognition of the correct fold, and not, as in CASP-3, alignment accuracy. Although some performance differences appeared within each of the four target categories used here, overall, no single server has proved markedly superior to the others. The results showed that current fully automated fold recognition servers can often identify remote similarities when pairwise sequence search methods fail. Nevertheless, in only a few cases outside the family-level targets has the score of the top-ranking fold been significant enough to allow for a confident fully automated prediction. Because the goals, rules, and procedures of CAFASP-1 were different from those used at CASP-3, the results reported here are not comparable with those reported in CASP-3. Nevertheless, it is clear that current automated fold recognition methods can not yet compete with "human-expert plus machine" predictions. Finally, CAFASP-1 has been useful in identifying the requirements for a future blind trial of automated served-based protein structure prediction.

Algorithms↗
PubMed1999

Metabolic changes in the brain of patients with anorexia and bulimia nervosa as detected by proton magnetic resonance spectroscopy.

OBJECTIVE: To investigate the brain of patients with anorexia and bulimia nervosa by localized proton magnetic resonance spectroscopy (1H-MRS) and to look for metabolic alterations. METHOD: Twenty patients with anorexia and bulimia nervosa were investigated by magnetic resonance imaging (MRI) and 1H-MRS in three regions of the brain. Age and sex-matched healthy subjects were investigated as controls. RESULTS: 1H-MRS revealed metabolic changes, such as a significant decrease of both myo-inositol and lipid compounds within the frontal white matter. The concentration of these compounds was further reduced with decreasing body mass index. Reduced lipid signals were also found in the occipital gray matter. In the cerebellum, the concentration of all metabolites including water, except lipids, was increased. DISCUSSION: The metabolic changes found in this study seem to be a consequence of nutritional deficiency. It has to be further investigated whether these findings have any relevance for brain function. 1H-MRS might serve as a valuable investigative tool to observe eating disorders as anorexia and bulimia nervosa and to follow the success of therapy.

Adolescent↗