scholarly journals Predicting primer and panel off-target rate in QIAseq targeted DNA panels using convolutional neural networks

2020 ◽  
Author(s):  
Chang Xu ◽  
Raghavendra Padmanabhan ◽  
Frank Reinecke ◽  
John DiCarlo ◽  
Yexun Wang
Keyword(s):  
Neural Network ◽  
Dna Sequences ◽  
Test Panel ◽  
True Value ◽  
The Neural Network ◽  
Target Template ◽  
Common Task ◽  
Target Dna ◽  
Target Binding ◽  
Target Rates

AbstractIn QIAseq targeted DNA panels, synthetic primers (short single-strand DNA sequences) are used for target enrichment via complementary DNA binding. Off-target priming could occur in this process when a primer binds to some loci where the DNA sequences are identical or very similar to the target template. These off-target DNA segments go through the rest of the workflow, wasting sequencing resources in unwanted regions. Off-target cannot be avoided if some segments of the target region are repetitive throughout the genome, nor can it be quantified until after sequencing. But if off-target rates can be prospectively predicted, scientists can make informed decisions about investment on high off-target panels.We developed pordle (predicting off-target rate with deep learning and epcr07), a convolutional neural network (CNN) model to predict off-target binding events of a given primer. The neural network was trained using 10 QIAseq DNA panels with 29,274 unique primers and then tested on an independent QIAseq panel with 7,576 primers. The model predicted a 10.5% off-target rate for the test panel, a -0.1% bias from the true value of 10.6%. The model successfully selected the better primer (in terms of off-target rate) for 89.2% of 3,835 pairs of close-by primers in the test panel whose off-target rates differ by at least 10%. The order-preserving property may help panel developers select the optimal primer from a group of candidates, which is a common task in panel design.

scholarly journals Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement

2021 ◽  
Vol 7 (8) ◽  
pp. eabe5496
Author(s):  
Evan A. Boyle ◽  
Winston R. Becker ◽  
Hua B. Bai ◽  
Janice S. Chen ◽  
Jennifer A. Doudna ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Dna Cleavage ◽  
High Specificity ◽  
Biophysical Model ◽  
Target Sequence ◽  
Sequence Context ◽  
Guide Rnas ◽  
Target Dna ◽  
Target Binding ◽  
Model Sequence

The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data have hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage and then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target modulates Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to “proofreading” capability. Lastly, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.

scholarly journals Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement

2020 ◽  
Author(s):  
Evan A Boyle ◽  
Winston R Becker ◽  
Hua B Bai ◽  
Janice S Chen ◽  
Jennifer A Doudna ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Dna Cleavage ◽  
High Specificity ◽  
Biophysical Model ◽  
Target Sequence ◽  
Sequence Context ◽  
Guide Rnas ◽  
Target Dna ◽  
Target Binding ◽  
Model Sequence

AbstractThe RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data has hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage, then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target significantly influences Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to “proofreading” capability. Finally, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.

Neural Network for Automatic Analysis of Motility Data

1994 ◽  
Vol 33 (01) ◽  
pp. 157-160 ◽  
Author(s):  
S. Kruse-Andersen ◽  
J. Kolberg ◽  
E. Jakobsen
Keyword(s):  
Neural Network ◽  
Muscular Activity ◽  
Recording System ◽  
Automatic Analysis ◽  
Biologically Relevant ◽  
System A ◽  
The Neural Network ◽  
Valuable Method ◽  
Motor Abnormalities ◽  
Trained Network

Abstract:Continuous recording of intraluminal pressures for extended periods of time is currently regarded as a valuable method for detection of esophageal motor abnormalities. A subsequent automatic analysis of the resulting motility data relies on strict mathematical criteria for recognition of pressure events. Due to great variation in events, this method often fails to detect biologically relevant pressure variations. We have tried to develop a new concept for recognition of pressure events based on a neural network. Pressures were recorded for over 23 hours in 29 normal volunteers by means of a portable data recording system. A number of pressure events and non-events were selected from 9 recordings and used for training the network. The performance of the trained network was then verified on recordings from the remaining 20 volunteers. The accuracy and sensitivity of the two systems were comparable. However, the neural network recognized pressure peaks clearly generated by muscular activity that had escaped detection by the conventional program. In conclusion, we believe that neu-rocomputing has potential advantages for automatic analysis of gastrointestinal motility data.

Decision Support for Psychiatric Diagnosis Based on a Simple Questionnaire

1997 ◽  
Vol 36 (04/05) ◽  
pp. 349-351
Author(s):  
H. Mizuta ◽  
K. Kawachi ◽  
H. Yoshida ◽  
K. Iida ◽  
Y. Okubo ◽  
...  
Keyword(s):  
Neural Network ◽  
Decision Support ◽  
Psychiatric Diagnosis ◽  
Psychiatric Patients ◽  
Bayesian Classifier ◽  
Neural Network Classifier ◽  
Correct Decision ◽  
Neurotic Disorders ◽  
The Neural Network

Abstract:This paper compares two classifiers: Pseudo Bayesian and Neural Network for assisting in making diagnoses of psychiatric patients based on a simple yes/no questionnaire which is provided at the outpatient’s first visit to the hospital. The classifiers categorize patients into three most commonly seen ICD classes, i.e. schizophrenic, emotional and neurotic disorders. One hundred completed questionnaires were utilized for constructing and evaluating the classifiers. Average correct decision rates were 73.3% for the Pseudo Bayesian Classifier and 77.3% for the Neural Network classifier. These rates were higher than the rate which an experienced psychiatrist achieved based on the same restricted data as the classifiers utilized. These classifiers may be effectively utilized for assisting psychiatrists in making their final diagnoses.

SCORING MODELING BASED ON NEURAL NETWORKS FOR DETERMINING A BANK BORROWER'S RATING

2020 ◽  
Vol 2020 (10) ◽  
pp. 54-62
Author(s):  
Oleksii VASYLIEV ◽  
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Network Architecture ◽  
Statistical Data ◽  
Activation Function ◽  
Decision Making Process ◽  
Neural Network Architecture ◽  
Acceptable Accuracy ◽  
The Neural Network ◽  
Sigmoid Activation Function

The problem of applying neural networks to calculate ratings used in banking in the decision-making process on granting or not granting loans to borrowers is considered. The task is to determine the rating function of the borrower based on a set of statistical data on the effectiveness of loans provided by the bank. When constructing a regression model to calculate the rating function, it is necessary to know its general form. If so, the task is to calculate the parameters that are included in the expression for the rating function. In contrast to this approach, in the case of using neural networks, there is no need to specify the general form for the rating function. Instead, certain neural network architecture is chosen and parameters are calculated for it on the basis of statistical data. Importantly, the same neural network architecture can be used to process different sets of statistical data. The disadvantages of using neural networks include the need to calculate a large number of parameters. There is also no universal algorithm that would determine the optimal neural network architecture. As an example of the use of neural networks to determine the borrower's rating, a model system is considered, in which the borrower's rating is determined by a known non-analytical rating function. A neural network with two inner layers, which contain, respectively, three and two neurons and have a sigmoid activation function, is used for modeling. It is shown that the use of the neural network allows restoring the borrower's rating function with quite acceptable accuracy.

Classification and Identification of Power System Disturbances Using Wavalet and Artificial Neural Network Technique

2005 ◽  
Vol 2 (2) ◽  
pp. 25
Author(s):  
Noraliza Hamzah ◽  
Wan Nor Ainin Wan Abdullah ◽  
Pauziah Mohd Arsad
Keyword(s):  
Neural Network ◽  
Power Quality ◽  
Probabilistic Neural Network ◽  
Microsoft Excel ◽  
Waveform Data ◽  
The Neural Network ◽  
Harmonic Voltage ◽  
Power Quality Disturbances ◽  
Electronic Load ◽  
Wavelet Technique

Power Quality disturbances problems have gained widespread interest worldwide due to the proliferation of power electronic load such as adjustable speed drives, computer, industrial drives, communication and medical equipments. This paper presents a technique based on wavelet and probabilistic neural network to detect and classify power quality disturbances, which are harmonic, voltage sag, swell and oscillatory transient. The power quality disturbances are obtained from the waveform data collected from premises, which include the UiTM Sarawak, Faculty of Science Computer in Shah Alam, Jati College, Menara UiTM, PP Seksyen 18 and Putra LRT. Reliable Power Meter is used for data monitoring and the data is further processed using the Microsoft Excel software. From the processed data, power quality disturbances are detected using the wavelet technique. After the disturbances being detected, it is then classified using the Probabilistic Neural Network. Sixty data has been chosen for the training of the Probabilistic Neural Network and ten data has been used for the testing of the neural network. The results are further interfaced using matlab script code.  Results from the research have been very promising which proved that the wavelet technique and Probabilistic Neural Network is capable to be used for power quality disturbances detection and classification.

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