One of the challenges in a viral pandemic is the emergence of novel variants with different phenotypical characteristics. An ability to forecast future viral individuals at the sequence level enables advance preparation by characterizing the sequences and closing vulnerabilities in current preventative and therapeutic methods. In this article, we explore, in the context of a viral pandemic, the problem of generating complete instances of undiscovered viral protein sequences, which have a high likelihood of being discovered in the future using protein language models. Current approaches to training these models fit model parameters to a known sequence set, which does not suit pandemic forecasting as future sequences differ from known sequences in some respects. To address this, we develop a novel method, called PandoGen, to train protein language models towards the pandemic protein forecasting task. PandoGen combines techniques such as synthetic data generation, conditional sequence generation, and reward-based learning, enabling the model to forecast future sequences, with a high propensity to spread. Applying our method to modeling the SARS-CoV-2 Spike protein sequence, we find empirically that our model forecasts twice as many novel sequences with five times the case counts compared to a model that is 30× larger. Our method forecasts unseen lineages months in advance, whereas models 4× and 30× larger forecast almost no new lineages. When trained on data available up to a month before the onset of important Variants of Concern, our method consistently forecasts sequences belonging to those variants within tight sequence budgets.

BACKGROUND: Modern Next Generation- and Third Generation- Sequencing methods such as Illumina and PacBio Circular Consensus Sequencing platforms provide accurate sequencing data. Parallel developments in Deep Learning have enabled the application of Deep Neural Networks to variant calling, surpassing the accuracy of classical approaches in many settings. DeepVariant, arguably the most popular among such methods, transforms the problem of variant calling into one of image recognition where a Deep Neural Network analyzes sequencing data that is formatted as images, achieving high accuracy. In this paper, we explore an alternative approach to designing Deep Neural Networks for variant calling, where we use meticulously designed Deep Neural Network architectures and customized variant inference functions that account for the underlying nature of sequencing data instead of converting the problem to one of image recognition. RESULTS: Results from 27 whole-genome variant calling experiments spanning Illumina, PacBio and hybrid Illumina-PacBio settings suggest that our method allows vastly smaller Deep Neural Networks to outperform the Inception-v3 architecture used in DeepVariant for indel and substitution-type variant calls. For example, our method reduces the number of indel call errors by up to 18%, 55% and 65% for Illumina, PacBio and hybrid Illumina-PacBio variant calling respectively, compared to a similarly trained DeepVariant pipeline. In these cases, our models are between 7 and 14 times smaller. CONCLUSIONS: We believe that the improved accuracy and problem-specific customization of our models will enable more accurate pipelines and further method development in the field. HELLO is available at https://github.com/anands-repo/hello.

While the Hidden Markov Model (HMM) is a versatile generative model of sequences capable of performing many exact inferences efficiently, it is not suited for capturing complex long-term structure in the data. Advanced state-space models based on Deep Neural Networks (DNN) overcome this limitation but cannot perform exact inferences. In this article, we present a new generative model for sequences that combines both aspects, the ability to perform exact inferences and the ability to model long-term structure, by augmenting the HMM with a deterministic, continuous state variable modeled through a Recurrent Neural Network. We empirically study the performance of the model on (i) synthetic data comparing it to the HMM, (ii) a supervised learning task in bioinformatics where it outperforms two DNN-based regressors and (iii) in the generative modeling of music where it outperforms many prominent DNN-based generative models.

k-mer counting is a popular pre-processing step in many bioinformatic algorithms. KMC2 is one of the most popular tools for k-mer counting. In this work, we leverage the computational power of the GPU to accelerate KMC2. Our goal is to reduce the overall runtime of many genome analysis tasks that use k-mer counting as an essential step. Compared to KMC2 running on a single CPU thread, our implementation using the GPU achieved 4.03x speedup when using one CPU thread, and 5.88x speedup when using four CPU threads. This speedup is significant because accelerating k-mer counting is challenging due to reasons like serialized portions of code and overhead of disk operations.

High-throughput techniques have revolutionized the study of genomics and molecular biology in recent years. These methods provide a large quantity of sequence data, and have applications in different areas of bioinformatics. One can sequence parts or whole of an organism's DNA to determine genetic information about an individual or a population, measure expression levels of different genes under different conditions, and determine binding affinity of proteins to DNA segments revealing details regarding gene regulation, at a higher resolution than before. However, different high-throughput methods that target even a single application have different underlying error models. Robust analytic pipelines are necessary to extract necessary information from the raw data. In this paper, we discuss future research directions for developing such analytics using techniques from Machine Learning and Deep Neural Networks. We focus on two applications that will affect the diagnosis and treatment of cancer.

FPGA is a promising candidate for the acceleration of Deep Neural Networks (DNN) with improved latency and energy consumption compared to CPU and GPU-based implementations. DNNs use sequences of layers of regular computation that are well suited for HLS-based design for FPGA. However, optimizing large neural networks under resource constraints is still a key challenge. HLS must manage on-chip computation, buffering resources, and off-chip memory accesses to minimize the total latency. In this paper, we present a design framework for DNNs that uses highly configurable IPs for neural network layers together with a new design space exploration engine for Resource Allocation Management (REALM). We also carry out efficient memory subsystem design and fixed-point weight re-training to further improve our FPGA solution. We demonstrate our design framework on the Long-term Recurrent Convolution Network for video inputs. Our implementation on a Xilinx VC709 board achieves 3.1X speedup compared to an NVIDIA K80 and 4.75X speedup compared to an Intel Xeon with 17.5X lower energy per image.

FPGAs have been rapidly adopted for acceleration of Deep Neural Networks (DNNs) with improved latency and energy efficiency compared to CPU and GPU-based implementations. High-level synthesis (HLS) is an effective design flow for DNNs due to improved productivity, debugging, and design space exploration ability. However, optimizing large neural networks under resource constraints for FPGAs is still a key challenge. In this paper, we present a series of effective design techniques for implementing DNNs on FPGAs with high performance and energy efficiency. These include the use of configurable DNN IPs, performance and resource modeling, resource allocation across DNN layers, and DNN reduction and re-training. We showcase several design solutions including Long-term Recurrent Convolution Network (LRCN) for video captioning, Inception module for FaceNet face recognition, as well as Long Short-Term Memory (LSTM) for sound recognition. These and other similar DNN solutions are ideal implementations to be deployed in vision or sound based IoT applications.

FPGAs have been rapidly adopted for acceleration of Deep Neural Networks (DNNs) with improved latency and energy efficiency compared to CPU and GPU-based implementations. High-level synthesis (HLS) is an effective design flow for DNNs due to improved productivity, debugging, and design space exploration ability. However, optimizing large neural networks under resource constraints for FPGAs is still a key challenge. In this paper, we present a series of effective design techniques for implementing DNNs on FPGAs with high performance and energy efficiency. These include the use of configurable DNN IPs, performance and resource modeling, resource allocation across DNN layers, and DNN reduction and re-training. We showcase several design solutions including Long-term Recurrent Convolution Network (LRCN) for video captioning, Inception module for FaceNet face recognition, as well as Long Short-Term Memory (LSTM) for sound recognition. These and other similar DNN solutions are ideal implementations to be deployed in vision or sound based IoT applications.

UNLABELLED: The most important features of error correction tools for sequencing data are accuracy, memory efficiency and fast runtime. The previous version of BLESS was highly memory-efficient and accurate, but it was too slow to handle reads from large genomes. We have developed a new version of BLESS to improve runtime and accuracy while maintaining a small memory usage. The new version, called BLESS 2, has an error correction algorithm that is more accurate than BLESS, and the algorithm has been parallelized using hybrid MPI and OpenMP programming. BLESS 2 was compared with five top-performing tools, and it was found to be the fastest when it was executed on two computing nodes using MPI, with each node containing twelve cores. Also, BLESS 2 showed at least 11% higher gain while retaining the memory efficiency of the previous version for large genomes. AVAILABILITY AND IMPLEMENTATION: Freely available at https://sourceforge.net/projects/bless-ec CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.