Maxim Borisyak

Nghia Duong-Trung, Stefan Born, Jong Woo Kim et al.

Machine learning (ML) is becoming increasingly crucial in many fields of engineering but has not yet played out its full potential in bioprocess engineering. While experimentation has been accelerated by increasing levels of lab automation, experimental planning and data modeling are still largerly depend on human intervention. ML can be seen as a set of tools that contribute to the automation of the whole experimental cycle, including model building and practical planning, thus allowing human experts to focus on the more demanding and overarching cognitive tasks. First, probabilistic programming is used for the autonomous building of predictive models. Second, machine learning automatically assesses alternative decisions by planning experiments to test hypotheses and conducting investigations to gather informative data that focus on model selection based on the uncertainty of model predictions. This review provides a comprehensive overview of ML-based automation in bioprocess development. On the one hand, the biotech and bioengineering community should be aware of the potential and, most importantly, the limitation of existing ML solutions for their application in biotechnology and biopharma. On the other hand, it is essential to identify the missing links to enable the easy implementation of ML and Artificial Intelligence (AI) tools in valuable solutions for the bio-community.

Maxim Borisyak, Stefan Born, Peter Neubauer et al.

Inferring parameters of macro-kinetic growth models, typically represented by Ordinary Differential Equations (ODE), from the experimental data is a crucial step in bioprocess engineering. Conventionally, estimates of the parameters are obtained by fitting the mechanistic model to observations. Fitting, however, requires a significant computational power. Specifically, during the development of new bioprocesses that use previously unknown organisms or strains, efficient, robust, and computationally cheap methods for parameter estimation are of great value. In this work, we propose using Deep Neural Networks (NN) for directly predicting parameters of mechanistic models given observations. The approach requires spending computational resources for training a NN, nonetheless, once trained, such a network can provide parameter estimates orders of magnitude faster than conventional methods. We consider a training procedure that combines Neural Networks and mechanistic models. We demonstrate the performance of the proposed algorithms on data sampled from several mechanistic models used in bioengineering describing a typical industrial batch process and compare the proposed method, a typical gradient-based fitting procedure, and the combination of the two. We find that, while Neural Network estimates are slightly improved by further fitting, these estimates are measurably better than the fitting procedure alone.

Christoph Lange, Isabel Thiele, Lara Santolin et al.

In biotechnology Raman Spectroscopy is rapidly gaining popularity as a process analytical technology (PAT) that measures cell densities, substrate- and product concentrations. As it records vibrational modes of molecules it provides that information non-invasively in a single spectrum. Typically, partial least squares (PLS) is the model of choice to infer information about variables of interest from the spectra. However, biological processes are known for their complexity where convolutional neural networks (CNN) present a powerful alternative. They can handle non-Gaussian noise and account for beam misalignment, pixel malfunctions or the presence of additional substances. However, they require a lot of data during model training, and they pick up non-linear dependencies in the process variables. In this work, we exploit the additive nature of spectra in order to generate additional data points from a given dataset that have statistically independent labels so that a network trained on such data exhibits low correlations between the model predictions. We show that training a CNN on these generated data points improves the performance on datasets where the annotations do not bear the same correlation as the dataset that was used for model training. This data augmentation technique enables us to reuse spectra as training data for new contexts that exhibit different correlations. The additional data allows for building a better and more robust model. This is of interest in scenarios where large amounts of historical data are available but are currently not used for model training. We demonstrate the capabilities of the proposed method using synthetic spectra of Ralstonia eutropha batch cultivations to monitor substrate, biomass and polyhydroxyalkanoate (PHA) biopolymer concentrations during of the experiments.

Maxim Borisyak, Stefan Born, Peter Neubauer et al.

Cultivation experiments often produce sparse and irregular time series. Classical approaches based on mechanistic models, like Maximum Likelihood fitting or Monte-Carlo Markov chain sampling, can easily account for sparsity and time-grid irregularities, but most statistical and Machine Learning tools are not designed for handling sparse data out-of-the-box. Among popular approaches there are various schemes for filling missing values (imputation) and interpolation into a regular grid (alignment). However, such methods transfer the biases of the interpolation or imputation models to the target model. We show that Deep Set Neural Networks equipped with triplet encoding of the input data can successfully handle bio-process data without any need for imputation or alignment procedures. The method is agnostic to the particular nature of the time series and can be adapted for any task, for example, online monitoring, predictive control, design of experiments, etc. In this work, we focus on forecasting. We argue that such an approach is especially suitable for typical cultivation processes, demonstrate the performance of the method on several forecasting tasks using data generated from macrokinetic growth models under realistic conditions, and compare the method to a conventional fitting procedure and methods based on imputation and alignment.

Artem Ryzhikov, Maxim Borisyak, Andrey Ustyuzhanin et al.

Anomaly detection is a challenging task that frequently arises in practically all areas of industry and science, from fraud detection and data quality monitoring to finding rare cases of diseases and searching for new physics. Most of the conventional approaches to anomaly detection, such as one-class SVM and Robust Auto-Encoder, are one-class classification methods, i.e. focus on separating normal data from the rest of the space. Such methods are based on the assumption of separability of normal and anomalous classes, and subsequently do not take into account any available samples of anomalies. Nonetheless, in practical settings, some anomalous samples are often available; however, usually in amounts far lower than required for a balanced classification task, and the separability assumption might not always hold. This leads to an important task -- incorporating known anomalous samples into training procedures of anomaly detection models. In this work, we propose a novel model-agnostic training procedure to address this task. We reformulate one-class classification as a binary classification problem with normal data being distinguished from pseudo-anomalous samples. The pseudo-anomalous samples are drawn from low-density regions of a normalizing flow model by feeding tails of the latent distribution into the model. Such an approach allows to easily include known anomalies into the training process of an arbitrary classifier. We demonstrate that our approach shows comparable performance on one-class problems, and, most importantly, achieves comparable or superior results on tasks with variable amounts of known anomalies.

Maxim Borisyak, Tatiana Gaintseva, Andrey Ustyuzhanin

Adversarial Optimization (AO) provides a reliable, practical way to match two implicitly defined distributions, one of which is usually represented by a sample of real data, and the other is defined by a generator. Typically, AO involves training of a high-capacity model on each step of the optimization. In this work, we consider computationally heavy generators, for which training of high-capacity models is associated with substantial computational costs. To address this problem, we introduce a novel family of divergences, which varies the capacity of the underlying model, and allows for a significant acceleration with respect to the number of samples drawn from the generator. We demonstrate the performance of the proposed divergences on several tasks, including tuning parameters of a physics simulator, namely, Pythia event generator.

Maxim Borisyak, Nikita Kazeev

Data analysis in high energy physics has to deal with data samples produced from different sources. One of the most widely used ways to unfold their contributions is the sPlot technique. It uses the results of a maximum likelihood fit to assign weights to events. Some weights produced by sPlot are by design negative. Negative weights make it difficult to apply machine learning methods. The loss function becomes unbounded. This leads to divergent neural network training. In this paper we propose a mathematically rigorous way to transform the weights obtained by sPlot into class probabilities conditioned on observables, thus enabling to apply any machine learning algorithm out-of-the-box.

Maxim Borisyak, Artem Ryzhikov, Andrey Ustyuzhanin et al.

Anomaly detection is not an easy problem since distribution of anomalous samples is unknown a priori. We explore a novel method that gives a trade-off possibility between one-class and two-class approaches, and leads to a better performance on anomaly detection problems with small or non-representative anomalous samples. The method is evaluated using several data sets and compared to a set of conventional one-class and two-class approaches.

Maxim Borisyak, Nikita Kazeev

Data analysis in high energy physics often deals with data samples consisting of a mixture of signal and background events. The sPlot technique is a common method to subtract the contribution of the background by assigning weights to events. Part of the weights are by design negative. Negative weights lead to the divergence of some machine learning algorithms training due to absence of the lower bound in the loss function. In this paper we propose a mathematically rigorous way to train machine learning algorithms on data samples with background described by sPlot to obtain signal probabilities conditioned on observables, without encountering negative event weight at all. This allows usage of any out-of-the-box machine learning methods on such data.

Maxim Borisyak, Andrey Ustyuzhanin, Denis Derkach et al.

High-energy physics experiments rely on reconstruction of the trajectories of particles produced at the interaction point. This is a challenging task, especially in the high track multiplicity environment generated by p-p collisions at the LHC energies. A typical event includes hundreds of signal examples (interesting decays) and a significant amount of noise (uninteresting examples). This work describes a modification of the Artificial Retina algorithm for fast track finding: numerical optimization methods were adopted for fast local track search. This approach allows for considerable reduction of the total computational time per event. Test results on simplified simulated model of LHCb VELO (VErtex LOcator) detector are presented. Also this approach is well-suited for implementation of paralleled computations as GPGPU which look very attractive in the context of upcoming detector upgrades.

Maxim Borisyak, Fedor Ratnikov, Denis Derkach et al.

Daily operation of a large-scale experiment is a challenging task, particularly from perspectives of routine monitoring of quality for data being taken. We describe an approach that uses Machine Learning for the automated system to monitor data quality, which is based on partial use of data qualified manually by detector experts. The system automatically classifies marginal cases: both of good an bad data, and use human expert decision to classify remaining "grey area" cases. This study uses collision data collected by the CMS experiment at LHC in 2010. We demonstrate that proposed workflow is able to automatically process at least 20\% of samples without noticeable degradation of the result.

Maxim Borisyak, Michail Usvyatsov, Michael Mulhearn et al.

The CRAYFIS experiment proposes to use privately owned mobile phones as a ground detector array for Ultra High Energy Cosmic Rays. Upon interacting with Earth's atmosphere, these events produce extensive particle showers which can be detected by cameras on mobile phones. A typical shower contains minimally-ionizing particles such as muons. As these particles interact with CMOS image sensors, they may leave tracks of faintly-activated pixels that are sometimes hard to distinguish from random detector noise. Triggers that rely on the presence of very bright pixels within an image frame are not efficient in this case. We present a trigger algorithm based on Convolutional Neural Networks which selects images containing such tracks and are evaluated in a lazy manner: the response of each successive layer is computed only if activation of the current layer satisfies a continuation criterion. Usage of neural networks increases the sensitivity considerably comparable with image thresholding, while the lazy evaluation allows for execution of the trigger under the limited computational power of mobile phones.

Maxim Borisyak, Roman Zykov, Artem Noskov

Classical approaches in recommender systems such as collaborative filtering are concentrated mainly on static user preference extraction. This approach works well as an example for music recommendations when a user behavior tends to be stable over long period of time, however the most common situation in e-commerce is different which requires reactive algorithms based on a short-term user activity analysis. This paper introduces a small mathematical framework for short-term user interest detection formulated in terms of item properties and its application for recommender systems enhancing. The framework is based on the fundamental concept of information theory --- Kullback-Leibler divergence.

Maxim Borisyak, Andrey Ustyuzhanin

The problem of autonomous navigation is one of the basic problems for robotics. Although, in general, it may be challenging when an autonomous vehicle is placed into partially observable domain. In this paper we consider simplistic environment model and introduce a navigation algorithm based on Learning Classifier System.