scholarly journals The generative capacity of probabilistic protein sequence models

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Francisco McGee ◽  
Sandro Hauri ◽  
Quentin Novinger ◽  
Slobodan Vucetic ◽  
Ronald M. Levy ◽  
...  
Keyword(s):  
Model Evaluation ◽  
Protein Sequence ◽  
Current Model ◽  
Higher Order ◽  
Fitness Landscapes ◽  
Generative Capacity ◽  
Potts Models ◽  
New Framework ◽  
Independent Model

AbstractPotts models and variational autoencoders (VAEs) have recently gained popularity as generative protein sequence models (GPSMs) to explore fitness landscapes and predict mutation effects. Despite encouraging results, current model evaluation metrics leave unclear whether GPSMs faithfully reproduce the complex multi-residue mutational patterns observed in natural sequences due to epistasis. Here, we develop a set of sequence statistics to assess the “generative capacity” of three current GPSMs: the pairwise Potts Hamiltonian, the VAE, and the site-independent model. We show that the Potts model’s generative capacity is largest, as the higher-order mutational statistics generated by the model agree with those observed for natural sequences, while the VAE’s lies between the Potts and site-independent models. Importantly, our work provides a new framework for evaluating and interpreting GPSM accuracy which emphasizes the role of higher-order covariation and epistasis, with broader implications for probabilistic sequence models in general.

scholarly journals Generative Capacity of Probabilistic Protein Sequence Models

2021 ◽  
Author(s):  
Francisco McGee ◽  
Quentin Novinger ◽  
Ronald Levy ◽  
Vincenzo Carnevale ◽  
Allan Haldane
Keyword(s):  
Protein Sequence ◽  
Probability Distributions ◽  
Higher Order ◽  
Generative Capacity ◽  
Synthetic Datasets ◽  
A Site ◽  
Order Sequence ◽  
New Framework ◽  
Independent Model

Abstract Potts models and variational autoencoders (VAEs) have recently gained popularity as generative protein sequence models (GPSMs) to explore fitness landscapes and predict the effect of mutations. Despite encouraging results, quantitative characterization and comparison of GPSM-generated probability distributions is still lacking. It is currently unclear whether GPSMs can faithfully reproduce the complex multi-residue mutation patterns observed in natural sequences arising due to epistasis. We develop a set of sequence statistics to comparatively assess the accuracy, or “generative capacity”, of three GPSMs: a pairwise Potts Hamiltonian, a vanilla VAE, and a site-independent model, using natural and synthetic datasets. We show that the generative capacity of the Potts Hamiltonian model is the largest; the higher order mutational statistics generated by the model agree with those observed for natural sequences. In contrast, we show that the vanilla VAE’s generative capacity lies between the pairwise Potts and site-independent models. Importantly, our work measures GPSM generative capacity in terms of higher-order sequence covariation and provides a new framework for evaluating and interpreting GPSM accuracy that emphasizes the role of epistasis.

Model of advanced training for general education managers in the context of educational reform in Vietnam

2020 ◽  
pp. 34-48
Author(s):  
Khoang Chung Khok
Keyword(s):  
General Education ◽  
Educational Reform ◽  
Current Model ◽  
Training Model ◽  
Educational Institutions ◽  
Current Period ◽  
Self Study ◽  
Manager Training ◽  
School Manager

With the requirement of fundamental and comprehensive reform of education, the coaching for managers in school is becoming urgent. The current model of regular coaching for managers in Vietnamese school is showing many shortcomings, failing to satisfy the requirements of educational reform in the current period. To solve this problem, different models and approaches may be used. The school manager training model using the LMS / TEMIS system is proposed to emphasize the role of self-study and selftraining; apply the achievements of information technology; promote the role of core educational managers and strengthen the relationships between leading experts at educational universities, academies of Vietnam and local educational institutions.

scholarly journals Dynamics of Extreme Stratospheric Negative Heat Flux Events in an Idealized Model

2018 ◽  
Vol 75 (10) ◽  
pp. 3521-3540 ◽  
Author(s):  
Etienne Dunn-Sigouin ◽  
Tiffany Shaw
Keyword(s):  
Heat Flux ◽  
Wave Propagation ◽  
Recent Work ◽  
Wave Interaction ◽  
Higher Order ◽  
Negative Events ◽  
Flow Mechanism ◽  
Mean Flow ◽  
Idealized Model

Recent work has shown that extreme stratospheric wave-1 negative heat flux events couple with the troposphere via an anomalous wave-1 signal. Here, a dry dynamical core model is used to investigate the dynamical mechanisms underlying the events. Ensemble spectral nudging experiments are used to isolate the role of specific dynamical components: 1) the wave-1 precursor, 2) the stratospheric zonal-mean flow, and 3) the higher-order wavenumbers. The negative events are partially reproduced when nudging the wave-1 precursor and the zonal-mean flow whereas they are not reproduced when nudging either separately. Nudging the wave-1 precursor and the higher-order wavenumbers reproduces the events, including the evolution of the stratospheric zonal-mean flow. Mechanism denial experiments, whereby one component is fixed to the climatology and others are nudged to the event evolution, suggest higher-order wavenumbers play a role by modifying the zonal-mean flow and through stratospheric wave–wave interaction. Nudging all tropospheric wave precursors (wave-1 and higher-order wavenumbers) confirms they are the source of the stratospheric waves. Nudging all stratospheric waves reproduces the tropospheric wave-1 signal. Taken together, the experiments suggest the events are consistent with downward wave propagation from the stratosphere to the troposphere and highlight the key role of higher-order wavenumbers.

Higher order neurons in buccal ganglia of Pleurobranchaea elicit vomiting motor activity

1983 ◽  
Vol 50 (3) ◽  
pp. 658-670 ◽  
Author(s):  
A. D. McClellan
Keyword(s):  
High Frequency ◽  
Motor Pattern ◽  
Higher Order ◽  
Root Activity ◽  
Command Neurons ◽  
Sensory Inputs ◽  
Buccal Ganglia ◽  
Output Pattern ◽  
Stimulation Of

The buccal mass of the gastropod Pleurobranchaea is used during a regurgitation response that consists of a writhing phase interrupted by brief periodic bouts of a vomiting phase (17, 20). During transitions from writhing to vomiting, specific changes occur in the motor pattern (19, 20). Evidence is presented suggesting that at least some of the initiation or "command" neurons for vomiting reside in the buccal ganglia. The present paper examines the role of two candidate vomiting-initiation cells, the ventral white cells (VWC) and midganglionic cells (MC), in the buccal ganglia of isolated nervous systems. Stimulation of single VWCs activates a vomiting motor pattern, consisting in part of alternating buccal root activity. Furthermore, the VWCs fire in high-frequency bursts during episodes (i.e., bouts) of this same vomiting pattern. Mutual reexcitation between the VWCs and motor pattern generator (MPG) appears to produce the accelerated buildup and maintenance of vomiting rhythms. Brief stimulation of single MCs "triggers" bouts of a vomiting motor pattern, but the membrane potential of this cell is only modulated during this same pattern, at least in the isolated nervous system. It is proposed that in intact animals the MCs are activated by sensory inputs and briefly excite the VWC-MPG network, thereby turning on the mutual reexcitatory mechanism mentioned above and switching the output pattern. A general implication for gastropod research is that higher order neurons that activate buccal root activity cannot automatically be given the function of "feeding command neuron," as some cells clearly control other responses, such as vomiting.

The Royal Commission on Historical Monuments (England)

Antiquity ◽  
1981 ◽  
Vol 55 (214) ◽  
pp. 106-114 ◽  
Author(s):  
P. J. Fowler
Keyword(s):  
Twentieth Century ◽  
Cultural Heritage ◽  
Royal Commission ◽  
Track Record ◽  
Original Title ◽  
Historical Monuments ◽  
Historic Monuments ◽  
New Framework

My original title deliberately contained several layers of ambiguity. First, my paper is official and ‘on the record’. Secondly, it refers incidentally to RCHM'S ‘track record’ and makes a few observations about the Commission's achievements and failures. Thirdly, and most importantly, it discusses the nature and future of that part of the national record of England's cultural heritage for which the Commission has the prime responsibility. That responsibility, implicit in the original 1908 Royal Warrant, and made explicit in its revised Warrant of 1963, involves the acquisition, storage and dissemination of information about the country's historic monuments and constructions in the widest sense of the phrase. The development of such a national record was envisaged by those who, in the later nineteenth and early twentieth centuries, agitated for the setting up of a Commission-type body. The record was to be the basis on which such a body could carry out its most pressing function, that is to assess the nation's monumental heritage in order to advise on what is worthy of preservation. A whole history could be written on how and why things turned out differently, but what I want to do here is to adumbrate the new framework for the changing emphases in the role of the Commission in the later twentieth century.

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