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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,009 records · Page 56

CMPLE: Correlation Modeling to Decode Photosynthesis Using the Minorize–Maximize Algorithm

In plant genomic experiments, correlations among various biological traits (phenotypes) give new insights into how genetic diversity may have tuned biological processes to enhance fitness under diverse conditions. Consequently, knowing how the correlations are affected by genetic (G) and environmental (E) factors helps develop climate-resilient plants. However, the current literature lacks any method for assessing the effect of predictors on pairwise correlations among multiple phenotypes together with easily interpretable model parameters. To address this need, we propose to model pairwise correlations directly in terms of G and E and develop a computationally efficient inference procedure. Two major novelties in our methodology are (1) the use of a composite pairwise likelihood method to avoid the positive definiteness restriction on the correlation matrix and (2) the use of a novel Minorize–Maximize (MM) algorithm for the efficient estimation of a large number of parameters. The proposed method shows excellent numerical performance on synthetic datasets. Here, the analysis of the motivating data on cowpea reveals that the rates of solar energy storage by photosynthesis (the aggregate trait) are differentially affected by different genetic loci through two distinct processes: “photoinhibition” which results from photodamage caused by excess light, and “photoprotection” which protects plants from photodamage but also results in energy loss.

Correlation modeling↗

Maast: genotyping thousands of microbial strains efficiently

Existing single nucleotide polymorphism (SNP) genotyping algorithms do not scale for species with thousands of sequenced strains, nor do they account for conspecific redundancy. Here we present a bioinformatics tool, Maast, which empowers population genetic meta-analysis of microbes at an unrivaled scale. Maast implements a novel algorithm to heuristically identify a minimal set of diverse conspecific genomes, then constructs a reliable SNP panel for each species, and enables rapid and accurate genotyping using a hybrid of whole-genome alignment and k-mer exact matching. We demonstrate Maast’s utility by genotyping thousands of Helicobacter pylori strains and tracking SARS-CoV-2 diversification.

59 BASIC BIOLOGICAL SCIENCES↗

Dynamics of genetic code evolution: The emergence of universality

We study the dynamics of genetic code evolution. The model of Vetsigian et al. [Proc. Natl. Acad. Sci. USA 103, 10696 (2006)] and Vetsigian [Collective evolution of biological and physical systems, Ph.D. thesis, 2005] uses the mechanism of horizontal gene transfer to demonstrate convergence of the genetic code to a near universal solution. We reproduce and analyze the algorithm as a dynamical system. All the parameters used in the model are varied to assess their impact on convergence and optimality score. We show that by allowing specific parameters to vary with time, the solution exhibits attractor dynamics. Finally, we study automorphisms of the genetic code arising due to this model. We use this to examine the scaling of the solutions to re-examine universality and find that there is a direct link to mutation rate.

59 BASIC BIOLOGICAL SCIENCES↗

Introducing GPU Acceleration into the Python-Based Simulations of Chemistry Framework

We introduce the first version of GPU4P Y SCF, a module that provides GPU acceleration of methods in P Y SCF. As a core functionality, this provides a GPU implementation of two-electron repulsion integrals (ERIs) for contracted basis sets comprising up to g functions using the Rys quadrature. As an illustration of how this can accelerate a quantum chemistry workflow, we describe how to use the ERIs efficiently in the integral-direct Hartree–Fock build and nuclear gradient construction. Benchmark calculations show a significant speedup of 2 orders of magnitude with respect to the multithreaded CPU Hartree–Fock code of P Y SCF and the performance comparable to other open-source GPU-accelerated quantum chemical packages, including GAMESS and QUICK, on a single NVIDIA A100 GPU.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A genomic data archive from the Network for Pancreatic Organ donors with Diabetes

The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.

59 BASIC BIOLOGICAL SCIENCES↗

Gene-by-environment interactions in plants: Molecular mechanisms, environmental drivers, and adaptive plasticity

Abstract Plants demonstrate a broad range of responses to environmental shifts. One of the most remarkable responses is plasticity, which is the ability of a single plant genotype to produce different phenotypes in response to environmental stimuli. As with all traits, the ability of plasticity to evolve depends on the presence of underlying genetic diversity within a population. A common approach for evaluating the role of genetic variation in driving differences in plasticity has been to study genotype-by-environment interactions (G × E). G × E occurs when genotypes produce different phenotypic trait values in response to different environments. In this review, we highlight progress and promising methods for identifying the key environmental and genetic drivers of G × E. Specifically, methodological advances in using algorithmic and multivariate approaches to understand key environmental drivers combined with new genomic innovations can greatly increase our understanding about molecular responses to environmental stimuli. These developing approaches can be applied to proliferating common garden networks that capture broad natural environmental gradients to unravel the underlying mechanisms of G × E. An increased understanding of G × E can be used to enhance the resilience and productivity of agronomic systems.

60 APPLIED LIFE SCIENCES↗

Hypergraph Random Walks, Laplacians, and Clustering

We propose a flexible framework for clustering hypergraph-structured data based on recently proposed random walks utilizing edge-dependent vertex weights. When incorporating edge-dependent vertex weights (EDVW), a weight is associated with each vertex-hyperedge pair, yielding a weighted incidence matrix of the hypergraph. Such weightings have been utilized in term-document representations of text data sets. We explain how random walks with EDVW serve to construct different hypergraph Laplacian matrices, and then develop a suite of clustering methods that use these incidence matrices and Laplacians for hypergraph clustering. Using 20Newsgroup, U.S. patent, Reuters' Corpus Volume 1, and genetics data sets, we compare the performance of these clustering algorithms experimentally against a variety of existing hypergraph clustering methods. We show that the proposed methods produce higher-quality clusters.

hypergraphs, clustering, laplacian, random walk, M↗

BubbleCluster v4

The BubbleCluster algorithm was developed to help address the limitations of traditional genetic mapping tools when presented with large amounts of data. The BubbleCluster software is a tool for the initial stage in the genetic mapping pipeline -- clustering genetic markers into linkage groups. BubbleCluster was designed to tackle large genetic marker data sets, and has been tested on input of up to 1.6M markers. Input format is identical to that of the popular MSTMap package, aiding useability.

Buluc, Aydin↗

Numerical Method for Fractional Advection-Diffusion Equation with Heredity

We propose a method of construction of difference schemes for fractional partial differential equations with delay in time. For the fractional equation with two-sided diffusion, fractional transfer in time, and a functional aftereffect, we construct an implicit difference scheme. We use the shifted Grünwald–Letnikov formulas for the approximation of fractional derivatives with respect to spatial variables and the L1-algorithm for the approximation of fractional derivatives in time. Also we use piecewise constant interpolation and extrapolation by extending the discrete prehistory of the model in time. The algorithm is a fractional analog of a purely implicit method; on each time step, it is reduced to the solution of linear algebraic systems. We prove the stability of the method and find its order of convergence.

97 MATHEMATICS AND COMPUTING↗

Multinode Multi-GPU Two-Electron Integrals: Code Generation Using the Regent Language

The computation of two-electron repulsion integrals (ERIs) is often the most expensive step of integral-direct self-consistent field methods. Formally it scales as O(N 4 ), where N is the number of Gaussian basis functions used to represent the molecular wave function. In practice, this scaling can be reduced to O(N 2 ) or less by neglecting small integrals with screening methods. The contributions of the ERIs to the Fock matrix are of Coulomb (J) and exchange (K) type and require separate algorithms to compute matrix elements efficiently. We previously implemented highly efficient GPU-accelerated J-matrix and K-matrix algorithms in the electronic structure code TeraChem. Although these implementations supported the use of multiple GPUs on a node, they did not support the use of multiple nodes. This presents a key bottleneck to cutting-edge ab initio simulations of large systems, e.g., excited state dynamics of photoactive proteins. We present our implementation of multinode multi-GPU J- and K-matrix algorithms in TeraChem using the Regent programming language. Regent directly supports distributed computation in a task-based model and can generate code for a variety of architectures, including NVIDIA GPUs. We demonstrate multinode scaling up to 45 GPUs (3 nodes) and benchmark against hand-coded TeraChem integral code. Finally, we also outline our metaprogrammed Regent implementation, which enables flexible code generation for integrals of different angular momenta.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Parallel replica dynamics method for bistable stochastic reaction networks: Simulation and sensitivity analysis

Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks. The proposed method uses parallel computing to accelerate the sampling of rare transitions. Furthermore, it can be combined with the path-space information bounds for parametric sensitivity analysis. With the proposed methodology, we study three bistable biological networks: the Schlögl model, the genetic switch network, and the enzymatic futile cycle network. We demonstrate the algorithmic speedup achieved in these numerical benchmarks. More significant acceleration is expected when multi-core or graphics processing unit computer architectures and programming tools such as CUDA are employed

97 MATHEMATICS AND COMPUTING↗

Scaling Out a Combinatorial Algorithm for Discovering Carcinogenic Gene Combinations to Thousands of GPUs

Cancer is a leading cause of death in the US, second only to heart disease. It is primarily a result of a combination of an estimated two-nine genetic mutations (multi-hit combinations). Although a body of research has identified hundreds of cancer-causing genetic mutations, we don’t know the specific combination of mutations responsible for specific instances of cancer for most cancer types. An approximate algorithm for solving the weighted set cover problem was previously adapted to identify combinations of genes with mutations that may be responsible for individual instances of cancer. However, the algorithm’s computational requirement scales exponentially with the number of genes, making it impractical for identifying more than three-hit combinations, even after the algorithm was parallelized and scaled up to a V100 GPU. Since most cancers have been estimated to require more than three hits, we scaled out the algorithm to identify combinations of four or more hits using 1000 nodes (6000 V100 GPUs with ≈48×106 processing cores) on the Summit supercomputer at Oak Ridge National Laboratory. Efficiently scaling out the algorithm required a series of algorithmic innovations and optimizations for balancing an exponentially divergent workload across processors and for minimizing memory latency and inter-node communication. We achieved an average strong scaling efficiency of 90.14% (80.96%–97.96% for 200 to 1000 nodes), compared to a 100 node run, with 84.18% scaling efficiency for 1000 nodes. With experimental validation, the multi-hit combinations identified here could provide further insight into the etiology of different cancer subtypes and provide a rational basis for targeted combination therapy.

Dash, Sajal↗

Optimizing Cell-based Antimicrobials through Pooled Genomic Libraries

DNA synthesis and assembly technologies ushered in through synthetic biology have great promise for biomanufacturing, bioremediation, and the development of living therapeutics. Unfortunately, predicting sequence to function relationships, including for biosynthetic pathways expressed in a new host organism, is difficult and often requires many iterative cycles of design, construction, and testing. We are working to develop data-driven approaches to identify the genetic determinants of growth defects and productivity for the expression of a cell-based antimicrobial. We assayed the growth, pigment production, and antimicrobial activity of a collection of over 10,000 genetic mutants of the violacein biosynthetic pathway and sequenced the genetic variation of these mutants. Through this project, we have developed an innovative codebase to automate the determination of pigmentation and antimicrobial clearing diameter for tens of thousands of genetic mutants cultivated on agar dishes. Further, we have written DNA sequence analysis code to demultiplex & provide consensus sequences from high-throughput PacBio long-read circular consensus sequencing (CCS) datasets. From this foundation, we plan to map DNA sequence to function to predict an optimal genetic design to maximize antimicrobial activity while minimizing deleterious growth effects. The workflows and algorithms developed through this project can be broadly applied to other engineered functions in microbes, uncovering sequence to function relationships for complex phenotypes where function impacts fitness.

59 BASIC BIOLOGICAL SCIENCES↗

Mathematical and Computational Challenges in Population Biology and Ecosystems Science

Mathematical and computational approaches provide powerful tools in the study of problems in population biology and ecosystems science. The subject has a rich history intertwined with the development of statistics and dynamical systems theory, but recent analytical advances, coupled with the enhanced potential of high-speed computation, have opened up new vistas and presented new challenges. Key challenges involve ways to deal with the collective dynamics of heterogeneous ensembles of individuals, and to scale from small spatial regions to large ones. The central issues-understanding how detail at one scale makes its signature felt at other scales, and how to relate phenomena across scales-cut across scientific disciplines and go to the heart of algorithmic development of approaches to high-speed computation. Examples are given from ecology, genetics, epidemiology, and immunology.

Levin, Simon A.↗

Issues in the analysis of oligonucleotide tiling microarrays for transcript mapping

Traditional microarrays use probes complementary to known genes to quantitate the differential gene expression between two or more conditions. Genomic tiling microarray experiments differ in that probes that span a genomic region at regular intervals are used to detect the presence or absence of transcription. This difference means the same sets of biases and the methods for addressing them are unlikely to be relevant to both types of experiment. We introduce the informatics challenges arising in the analysis of tiling microarray experiments as open problems to the scientific community and present initial approaches for the analysis of this nascent technology.

Review↗

rBahadur: efficient simulation of structured high-dimensional genotype data with applications to assortative mating

Existing methods for generating synthetic genotype data are ill-suited for replicating the effects of assortative mating (AM). We propose rb_dplr, a novel and computationally efficient algorithm for generating high-dimensional binary random variates that effectively recapitulates AM-induced genetic architectures using the Bahadur order-2 approximation of the multivariate Bernoulli distribution. The rBahadur R library is available through the Comprehensive R Archive Network at https://CRAN.R-project.org/package=rBahadur.

59 BASIC BIOLOGICAL SCIENCES↗

DyG-DPCD: A Distributed Parallel Community Detection Algorithm for Large-Scale Dynamic Graphs

Dynamic (Temporal) graphs capture the valuable evolution of real-world systems, from the continuously evolving patterns of social interactions and genetic pathways to the dynamic fluctuations of economic forces. Detecting communities for such evolving networks poses unique challenges. Detecting and analyzing the evolution of communities within dynamic graphs unlocks valuable insights into the underlying structural and temporal patterns of real-world systems. However, the sheer volume of modern graph data and the inherent complexity of the temporal dimension pose significant challenges to scalable community detection algorithms. Addressing this gap, our work explores the limited landscape of scalable distributed-memory parallel methods specifically designed for dynamic network community detection. We propose a novel parallel algorithm, DyG-DPCD (Dynamic Graph Distributed Parallel Community Detection), to detect communities in dynamic networks using the Message Passing Interface (MPI) framework. We present a vertex-centric approach, allowing us to detect communities through local optimization. Furthermore, we enhance our baseline algorithm by incorporating three heuristics, which improve the algorithm’s performance significantly while maintaining the quality of the solutions. We demonstrate the efficiency of our algorithm by experimenting on several real-world large-scale networks with hundreds of millions of edges spanning diverse domains. Notably, DyG-DPCD achieves speedups between 25× and 30× for large networks that we experimented on using NERSC compute nodes. In conclusion, our algorithm outperforms the STINGER parallel re-agglomeration algorithm by 30×.

97 MATHEMATICS AND COMPUTING↗