scholarly journals Software for the analysis and visualization of deep mutational scanning data

2015 ◽  
Author(s):  
Jesse D Bloom

BackgroundDeep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.ResultsI describe a software package,dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show thatdms_toolsyields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Usingdms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures. The preferences and their changes can be intuitively visualized with sequence-logo-style plots created using an extension toweblogo.Conclusionsdms_toolsimplements a statistically principled approach for the analysis and subsequent visualization of deep mutational scanning data.

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12463 ◽  
Author(s):  
Morgane Rolland ◽  
Jonathan M. Carlson ◽  
Siriphan Manocheewa ◽  
J. Victor Swain ◽  
Erinn Lanxon-Cookson ◽  
...  

1990 ◽  
Vol 22 (3) ◽  
pp. 209-210 ◽  
Author(s):  
PEGGY A. MILLER-GRABER ◽  
LAURIE M. LAWRENCE ◽  
ELAINE KURCZ ◽  
RACHEL KANE ◽  
KARIN BUMP ◽  
...  

1985 ◽  
Vol 5 (10-11) ◽  
pp. 855-865 ◽  
Author(s):  
L. Ping Chung ◽  
Kenneth B. M. Reid

The binding and cofactor activities of C4b-binding protein were examined before and after limited proteolysis by pepsin, trypsin and chymotrypsin. The major fragments generated were characterized by amino acid sequencing, thus establishing the precise points of limited proteolysis. These studies allow a tentative assignment of the cofactor activity site to the residues 177–322 of the 549 amino acid long chain of C4b-binding protein but indicated that residues in the region 332–395 are important in the binding activity.


2017 ◽  
Vol 79 (6) ◽  
pp. 1003-1012 ◽  
Author(s):  
Kiran PANDEY ◽  
Yoichi MIZUKAMI ◽  
Kenji WATANABE ◽  
Syuiti SAKAGUTI ◽  
Hiroya KADOKAWA

2019 ◽  
Author(s):  
Manvi Sharma ◽  
Kavita Isvaran

AbstractWhen a strong selection pressure, such as predation risk, varies widely in space and time, how should prey respond? When risk varies predictably, prey are hypothesized to respond in a risk-sensitive manner. It is less clear how prey should respond when risk varies unpredictably.Additionally, prey response may also depend on how predation risk interacts with other selection pressures. Our understanding of the complex action of multiple and variable selection pressures on prey traits is still comparatively poor. Here, we examine how predictable and unpredictable aspects of predation risk act together with another important selection pressure to influence prey behaviour in the rock pool breeding mosquito, Aedes vexans. Through the selection of sites for oviposition, female mosquitoes can influence the predation risk faced by their offspring. We tested how females select oviposition sites, when encountering pools that vary in larval predation risk and desiccation risk. We comprehensively quantified spatial and temporal variation in predation risk by measuring densities of predatory dragonfly nymphs in rock pools of different sizes, along the mosquito breeding season. We also measured hydroperiod length. We next conducted manipulative experiments in rock pools and measured female oviposition responses to variation in predation and desiccation risks. Predation risk varied widely in space and time. Desiccation risk only appeared important for the small pools. Ovipositing females appeared to respond to these multiple aspects of variation in selection pressures. Females seemed to respond to predictable variation by avoiding large pools that permanently harboured predators in natural settings. Female responses were more variable to medium-sized pools with naturally stochastic predator densities, highlighting the role of unpredictability in predation risk in shaping behaviour. Females did not clearly prefer small pools that were naturally devoid of predators but carried high desiccation risk, suggesting that they balance multiple risks – predation versus desiccation – when choosing oviposition sites. Our study suggests that wild populations may commonly experience multiple and variable selection pressures that can favour seemingly puzzling trait variation. We highlight the need to quantify variation in selection pressures and investigate how such variation, especially the unpredictable aspects, shapes prey traits.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Bargavi Thyagarajan ◽  
Jesse D Bloom

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.


Metabolites ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 114 ◽  
Author(s):  
Kristen Clermont ◽  
Yaxin Wang ◽  
Siming Liu ◽  
Zhenzhen Yang ◽  
Claude dePamphilis ◽  
...  

Parasitic weeds of the family Orobanchaceae attach to the roots of host plants via haustoria capable of drawing nutrients from host vascular tissue. The connection of the haustorium to the host marks a shift in parasite metabolism from autotrophy to at least partial heterotrophy, depending on the level of parasite dependence. Species within the family Orobanchaceae span the spectrum of host nutrient dependency, yet the diversity of parasitic plant metabolism remains poorly understood, particularly during the key metabolic shift surrounding haustorial attachment. Comparative profiling of major metabolites in the obligate holoparasite Phelipanche aegyptiaca and the facultative hemiparasite Triphysaria versicolor before and after attachment to the hosts revealed several metabolic shifts implicating remodeling of energy and amino acid metabolism. After attachment, both parasites showed metabolite profiles that were different from their respective hosts. In P. aegyptiaca, prominent changes in metabolite profiles were also associated with transitioning between different tissue types before and after attachment, with aspartate levels increasing significantly after the attachment. Based on the results from 15N labeling experiments, asparagine and/or aspartate-rich proteins were enriched in host-derived nitrogen in T. versicolor. These results point to the importance of aspartate and/or asparagine in the early stages of attachment in these plant parasites and provide a rationale for targeting aspartate-family amino acid biosynthesis for disrupting the growth of parasitic weeds.


1957 ◽  
Vol 35 (1) ◽  
pp. 1005-1016 ◽  
Author(s):  
J. B. Derrick ◽  
Audrey P. Hanley

Observations have been made on the specific free amino acids (chromatographic analysis) and other nitrogenous constituents in the serum and urine of normal and arthritic men under controlled dietary conditions, before and after a glycine load and adrenocorticotropin administered separately and together.Differences in the metabolism of amino acids between normal individuals and arthritics, particularly of alanine, proline, glutamic acid, taurine, and possibly tyrosine (and/or tryptophan) and cystine, were apparent. The differences were largely confined to the non-essential amino acids. Concomitant increases seen in the serum levels and in the excretion of several amino acids, in response to a load of a single amino acid, indicate that the increases in excretion are more than a matter of competition for reabsorption in the kidney. A prerenal phenomenon appears to be involved, possibly interconversion of amino acids. This concept is supported by the evidence that the increases in the serum levels were restricted to the non-essential amino acids.


1957 ◽  
Vol 35 (11) ◽  
pp. 1005-1016 ◽  
Author(s):  
J. B. Derrick ◽  
Audrey P. Hanley

Observations have been made on the specific free amino acids (chromatographic analysis) and other nitrogenous constituents in the serum and urine of normal and arthritic men under controlled dietary conditions, before and after a glycine load and adrenocorticotropin administered separately and together.Differences in the metabolism of amino acids between normal individuals and arthritics, particularly of alanine, proline, glutamic acid, taurine, and possibly tyrosine (and/or tryptophan) and cystine, were apparent. The differences were largely confined to the non-essential amino acids. Concomitant increases seen in the serum levels and in the excretion of several amino acids, in response to a load of a single amino acid, indicate that the increases in excretion are more than a matter of competition for reabsorption in the kidney. A prerenal phenomenon appears to be involved, possibly interconversion of amino acids. This concept is supported by the evidence that the increases in the serum levels were restricted to the non-essential amino acids.


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