On the predictive power of sequence similarity in yeast

2001 ◽  
Author(s):  
Yonatan Bilu ◽  
Michal Linial
Keyword(s):  
Predictive Power ◽  
Sequence Similarity

scholarly journals Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity

2019 ◽  
Author(s):  
Neerja Thakkar ◽  
Chris Bailey-Kellogg
Keyword(s):  
Predictive Power ◽  
Sequence Similarity ◽  
Structural Similarity ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
The Third ◽  
Repertoire Sequencing ◽  
Complementarity Determining Regions ◽  
Cellular Immune

AbstractRepertoire sequencing is enabling deep explorations into the cellular immune response, including the characterization of commonalities and differences among T cell receptor (TCR) repertoires from different individuals, pathologies, and antigen specificities. In seeking to understand the generality of patterns observed in different groups of TCRs, it is necessary to balance how well each pattern represents the diversity among TCRs from one group (sensitivity) vs. how many TCRs from other groups it also represents (specificity). The variable complementarity determining regions (CDRs), particularly the third CDRs (CDR3s) interact with MHC-presented epitopes from putative antigens, and thus encode the determinants of recognition. We here systematically characterize the predictive power that can be obtained from CDR3 sequences, using representative, readily interpretable methods for evaluating CDR sequence similarity and then clustering and classifying sequences based on similarity. An initial analysis of CDR3s of known structure, clustered by structural similarity, helps calibrate the limits of sequence diversity among CDRs that might have a common mode of interaction with presented epitopes. Subsequent analyses demonstrate that this same range of sequence similarity strikes an appropriate specificity/sensitivity balance in distinguishing twins from non-twins based on overall CDR3 repertoires, classifying CDR3 repertoires by antigen specificity, and distinguishing general pathologies. We conclude that within this fairly broad range of sequence similarity, matching CDR3 sequences are likely to share specificities.

scholarly journals Functional Analysis of Enzyme Families Using Residue-Residue Coevolution Similarity Networks

2019 ◽  
Author(s):  
Christian Atallah ◽  
David James Skelton ◽  
Simon J. Charnock ◽  
Anil Wipat
Keyword(s):  
Functional Analysis ◽  
Substrate Specificity ◽  
Predictive Power ◽  
Structural Information ◽  
Sequence Similarity ◽  
Topological Analysis ◽  
Label Propagation ◽  
Similarity Networks ◽  
Enzyme Families ◽  
Sequence Similarity Networks

AbstractMotivationResidue-residue coevolution has been used to elucidate structural information of enzymes. Networks of coevolution patterns have also been analyzed to discover residues important for the function of individual enzymes. In this work, we take advantage of the functional importance of coevolving residues to perform network-based clustering of subsets of enzyme families based on similarities of their coevolution patterns, or “Coevolution Similarity Networks”. The power of these networks in the functional analysis of sets of enzymes is explored in detail, using Sequence Similarity Networks as a benchmark.ResultsA novel method to produce protein-protein networks showing the similarity between proteins based on the matches in the patterns of their intra-residue residue coevolution is described. The properties of these co-evolution similarity networks (CSNs) was then explored, especially in comparison to widely used sequence similarity networks (SSNs). We focused on the predictive power of CSNs and SSNs for the annotation of enzyme substrate specificity in the form of Enzyme Commission (EC) numbers using a label propagation approach. A method for systematically defining the threshold necessary to produce the optimally predictive CSNs and SSNs is described. Our data shows that, for the two protein families we analyse, CSNs show higher predictive power for the reannotation of substrate specificity for previously annotated enzymes retrieved from Swissprot. A topological analysis of both CSNs and SSNs revealed core similarities in the structure, topology and annotation distribution but also reveals a subset of nodes and edges that are unique to each network type, highlighting their complementarity. Overall, we propose CSNs as a new method for analysing the function enzyme families that complements, and offers advantages to, other network based methods for protein family analysis.AvailabilitySource code available on request.

scholarly journals Systematic bacterialization of yeast genes identifies a near-universally swappable pathway

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Aashiq H Kachroo ◽  
Jon M Laurent ◽  
Azat Akhmetov ◽  
Madelyn Szilagyi-Jones ◽  
Claire D McWhite ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Growth Rate ◽  
Predictive Power ◽  
Common Ancestor ◽  
Sequence Similarity ◽  
Growth Defect ◽  
Biosynthesis Pathway ◽  
Mitochondrial Localization ◽  
Bacterial Genes ◽  
Yeast Genes

Eukaryotes and prokaryotes last shared a common ancestor ~2 billion years ago, and while many present-day genes in these lineages predate this divergence, the extent to which these genes still perform their ancestral functions is largely unknown. To test principles governing retention of ancient function, we asked if prokaryotic genes could replace their essential eukaryotic orthologs. We systematically replaced essential genes in yeast by their 1:1 orthologs from Escherichia coli. After accounting for mitochondrial localization and alternative start codons, 31 out of 51 bacterial genes tested (61%) could complement a lethal growth defect and replace their yeast orthologs with minimal effects on growth rate. Replaceability was determined on a pathway-by-pathway basis; codon usage, abundance, and sequence similarity contributed predictive power. The heme biosynthesis pathway was particularly amenable to inter-kingdom exchange, with each yeast enzyme replaceable by its bacterial, human, or plant ortholog, suggesting it as a near-universally swappable pathway.

Communicating the predictive power of selection and admissions measures

2008 ◽  
Author(s):  
Sara Cooper ◽  
Nathan Kuncel ◽  
Kara Siegert
Keyword(s):  
Predictive Power

GB Virus C/Hepatitis G Virus Isolates in Japanese Haemophiliacs and their Origins

1998 ◽  
Vol 80 (08) ◽  
pp. 242-245 ◽  
Author(s):  
Yoshihide Fukuda ◽  
Tetsuo Hayakawa ◽  
Junki Takamatsu ◽  
Hidehiko Saito ◽  
Hiroaki Okamoto ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
West African ◽  
Blood Products ◽  
Hepatitis G Virus ◽  
Gb Virus C ◽  
Route Of Transmission ◽  
Polymerase Chain ◽  
Hepatitis G ◽  
Virus C ◽  
Virus Isolates

SummaryJapanese haemophiliacs have been at high risk for infection with parenterally-transmissible viruses through the use of blood products, especially imported ones. Recently, novel transfusion-transmissible virus, GB virus C (GBV-C)/hepatitis G virus (HGV) were isolated. We investigated the origin and route of transmission of GBV-C/HGV isolates in haemophiliacs in Japan. GBV-C/HGV RNA was measured by nested reverse transcription polymerase chain reaction in 91 Japanese haemophiliacs. Phylogenetic analysis and genotypic grouping of GBV-C/HGV isolates in Japanese haemophiliacs were performed based on sequences in the 5’ untranslated region, and the characteristics were compared with those of reported isolates. GBV-C/HGV infection was present in 19 of 91 haemophiliacs (20.9%). Sequence analysis showed that 15 of the 19 isolates (78.9%) showed sequence similarity to a group in which mainly West African isolates have been reported. The other 4 isolates (21.1%) showed sequence similarity to Asian isolates. None of the GBV-C/HGV isolates showed sequences similar to those generally found in isolates from USA and Europe. The majority of GBV-C/HGV isolates found in Japanese haemophiliacs who are considered to have been infected by imported blood products were similar to those detected in West Africa.

A Comparison of the Effect of Decorsin and Two Disintegrins, Albolabrin and Eristostatin, on Platelet Function

1995 ◽  
Vol 74 (05) ◽  
pp. 1316-1322 ◽  
Author(s):  
Mary Ann McLane ◽  
Jagadeesh Gabbeta ◽  
A Koneti Rao ◽  
Lucia Beviglia ◽  
Robert A Lazarus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Sequence Similarity ◽  
Platelet Aggregation Inhibitors ◽  
Antiplatelet Drug ◽  
Rgd Sequence ◽  
Fibrinogen Receptor ◽  
Activated Platelets

SummaryNaturally-occurring fibrinogen receptor antagonists and platelet aggregation inhibitors that are found in snake venom (disintegrins) and leeches share many common features, including an RGD sequence, high cysteine content, and low molecular weight. There are, however, significant selectivity and potency differences. We compared the effect of three proteins on platelet function: albolabrin, a 7.5 kDa disintegrin, eristostatin, a 5.4 kDa disintegrin in which part of the disintegrin domain is deleted, and decorsin, a 4.5 kDa non-disintegrin derived from the leech Macrobdella decora, which has very little sequence similarity with either disintegrin. Decorsin was about two times less potent than albolabrin and six times less potent than eristostatin in inhibiting ADP- induced human platelet aggregation. It had a different pattern of interaction with glycoprotein IIb/IIIa as compared to the two disintegrins. Decorsin bound with a low affinity to resting platelets (409 nM) and to ADP-activated platelets (270 nM), and with high affinity to thrombin- activated platelets (74 nM). At concentrations up to 685 nM, it did not cause expression of a ligand-induced binding site epitope on the (β3 subunit of the GPIIb/IIIa complex. It did not significantly inhibit isolated GPIIb/IIIa binding to immobilized von Willebrand Factor. At low doses (1.5-3.0 μg/mouse), decorsin protected mice against death from pulmonary thromboembolism, showing an effect similar to eristostatin. This suggested that decorsin is a much more potent inhibitor of platelet aggregation in vivo than in vitro, and it may have potential as an antiplatelet drug.

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