Rapid technological advancements in sequencing technologies allow producing cost effective and high volume sequencing data. Processing this data for real-time clinical diagnosis is potentially time-consuming if done on a single computing node. This work presents a complete variant calling workflow, implemented using the Message Passing Interface (MPI) to leverage the benefits of high bandwidth interconnects. This solution (GenMPI) is portable and flexible, meaning it can be deployed to any private or public cluster/cloud infrastructure. Any alignment or variant calling application can be used with minimal adaptation. To achieve high performance, compressed input data can be streamed in parallel to alignment applications while uncompressed data can use internal file seek functionality to eliminate the bottleneck of streaming input data from a single node. Alignment output can be directly stored in multiple chromosome-specific SAM files or a single SAM file. After alignment, a distributed queue using MPI RMA (Remote Memory Access) atomic operations is created for sorting, indexing, marking of duplicates (if necessary) and variant calling applications. We ensure the accuracy of variants as compared to the original single node methods. We also show that for 300x coverage data, alignment scales almost linearly up to 64 nodes (8192 CPU cores). Overall, this work outperforms existing Big Data based workflows by a factor of two and is almost 20% faster than other MPI-based implementations for alignment without any extra memory overheads. Sorting, indexing, duplicate removal and variant calling is also scalable up to 8 nodes cluster. For pair-end short-reads (Illumina) data, we integrated the BWA-MEM aligner and three variant callers (GATK HaplotypeCaller, DeepVariant and Octopus), while for long-reads data, we integrated the Minimap2 aligner and three different variant callers (DeepVariant, DeepVariant with WhatsHap for phasing (PacBio) and Clair3 (ONT)).

Moving structured data between different big data frameworks and/or data warehouses/storage systems often cause significant overhead. Most of the time more than 80% of the total time spent in accessing data is elapsed in serialization/de-serialization step. Columnar data formats are gaining popularity in both analytics and transactional databases. Apache Arrow, a unified columnar in-memory data format promises to provide efficient data storage, access, manipulation and transport. In addition, with the introduction of the Arrow Flight communication capabilities, which is built on top of gRPC, Arrow enables high performance data transfer over TCP networks. Arrow Flight allows parallel Arrow RecordBatch transfer over networks in a platform and language-independent way, and offers high performance, parallelism and security based on open-source standards. In this paper, we bring together some recently implemented use cases of Arrow Flight with their benchmarking results. These use cases include bulk Arrow data transfer, querying subsystems and Flight as a microservice integration into different frameworks to show the throughput and scalability results of this protocol. We show that Flight is able to achieve up to 6000 MB/s and 4800 MB/s throughput for DoGet() and DoPut() operations respectively. On Mellanox ConnectX-3 or Connect-IB interconnect nodes Flight can utilize upto 95% of the total available bandwidth. Flight is scalable and can use upto half of the available system cores efficiently for a bidirectional communication. For query systems like Dremio, Flight is order of magnitude faster than ODBC and turbodbc protocols. Arrow Flight based implementation on Dremio performs 20x and 30x better as compared to turbodbc and ODBC connections respectively. We briefly outline some recent Flight based use cases both in big data frameworks like Apache Spark and Dask and remote Arrow data processing tools. We also discuss some limitations and future outlook of Apache Arrow and Arrow Flight as a whole.

The rapidly growing size of genomics data bases, driven by advances in sequencing technologies, demands fast and cost-effective processing. However, processing this data creates many challenges, particularly in selecting appropriate algorithms and computing platforms. Computing systems need data closer to the processor for fast processing. Traditionally, due to cost, volatility and other physical constraints of DRAM, it was not feasible to place large amounts of working data sets in memory. However, new emerging storage class memories allow storing and processing big data closer to the processor. In this work, we show how the commonly used genomics data format, Sequence Alignment/Map (SAM), can be presented in the Apache Arrow in-memory data representation to benefit of in-memory processing and to ensure better scalability through shared memory objects, by avoiding large (de)-serialization overheads in cross-language interoperability. To demonstrate the benefits of such a system, we propose ArrowSAM, an in-memory SAM format that uses the Apache Arrow framework, and integrate it into genome pre-processing pipelines including BWA-MEM, Picard and Sambamba. Results show 15x and 2.4x speedups as compared to Picard and Sambamba, respectively. The code and scripts for running all workflows are freely available at https://github.com/abs-tudelft/ArrowSAM.

Background: Immense improvements in sequencing technologies enable producing large amounts of high throughput and cost effective next-generation sequencing (NGS) data. This data needs to be processed efficiently for further downstream analyses. Computing systems need this large amounts of data closer to the processor (with low latency) for fast and efficient processing. However, existing workflows depend heavily on disk storage and access, to process this data incurs huge disk I/O overheads. Previously, due to the cost, volatility and other physical constraints of DRAM memory, it was not feasible to place large amounts of working data sets in memory. However, recent developments in storage-class memory and non-volatile memory technologies have enabled computing systems to place huge data in memory to process it directly from memory to avoid disk I/O bottlenecks. To exploit the benefits of such memory systems efficiently, proper formatted data placement in memory and its high throughput access is necessary by avoiding (de)-serialization and copy overheads in between processes. For this purpose, we use the newly developed Apache Arrow, a cross-language development framework that provides language-independent columnar in-memory data format for efficient in-memory big data analytics. This allows genomics applications developed in different programming languages to communicate in-memory without having to access disk storage and avoiding (de)-serialization and copy overheads. Implementation: We integrate Apache Arrow in-memory based Sequence Alignment/Map (SAM) format and its shared memory objects store library in widely used genomics high throughput data processing applications like BWA-MEM, Picard and GATK to allow in-memory communication between these applications. In addition, this also allows us to exploit the cache locality of tabular data and parallel processing capabilities through shared memory objects. Results: Our implementation shows that adopting in-memory SAM representation in genomics high throughput data processing applications results in better system resource utilization, low number of memory accesses due to high cache locality exploitation and parallel scalability due to shared memory objects. Our implementation focuses on the GATK best practices recommended workflows for germline analysis on whole genome sequencing (WGS) and whole exome sequencing (WES) data sets. We compare a number of existing in-memory data placing and sharing techniques like ramDisk and Unix pipes to show how columnar in-memory data representation outperforms both. We achieve a speedup of 4.85x and 4.76x for WGS and WES data, respectively, in overall execution time of variant calling workflows. Similarly, a speedup of 1.45x and 1.27x for these data sets, respectively, is achieved, as compared to the second fastest workflow. In some individual tools, particularly in sorting, duplicates removal and base quality score recalibration the speedup is even more promising. Availability: The code and scripts used in our experiments are available in both container and repository form at: https://github.com/abs-tudelft/ArrowSAM.