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Results for “sequence analysis”

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 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes

Recent genome projects for ctenophores have revealed the presence of numerous ionotropic glutamate receptors (iGluRs) in Mnemiopsis leidyi and Pleurobrachia bachei, among our earliest metazoan ancestors. Sequence alignments and phylogenetic analysis show that these form a distinct clade from the well-characterized AMPA, kainate, and NMDA iGluR subtypes found in vertebrates. Although annotated as glutamate and kainate receptors, crystal structures of the ML032222a and PbiGluR3 ligand-binding domains (LBDs) reveal endogenous glycine in the binding pocket, whereas ligand-binding assays show that glycine binds with nanomolar affinity; biochemical assays and structural analysis establish that glutamate is occluded from the binding cavity. Further analysis reveals ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunits that bind glycine, but also a conserved disulfide in loop 1 of the LBD that is found in all vertebrate NMDA but not AMPA or kainate receptors. In this paper, we hypothesize that ctenophore iGluRs are related to an early ancestor of NMDA receptors, suggesting a common evolutionary path for ctenophores and bilaterian species, and finally suggest that future work should consider both glycine and glutamate as candidate neurotransmitters in ctenophore species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability

Weakening of synaptic transmission at theDrosophilalarval neuromuscular junction triggers two forms of homeostatic compensation, one that increases the probability of glutamate release per action potential (P r ) and another that increases motoneuron (MN) activity. We investigated the molecular changes in MNs that underlie the increase in MN activity. RNA sequencing (RNA-seq) analysis on MNs whose glutamate release is weakened by knockdown of components of the MN transmitter release machinery reveals a reduction in expression of a group of genes that encode potassium channels and their positive modulators. These results identify a mechanism of compensation for weakened synaptic transmission by MNs, which engages a transcriptional program in those cells to increase firing and, thereby, ensure sufficient locomotory drive.

Science & Technology - Other Topics↗
DOE OSTI2026

GenomeDepot: data management system for microbial comparative genomics

Summary GenomeDepot is an open-source web-based platform for annotation, management, and comparative analysis of microbial genomic sequences and associated data including ortholog families, protein domains, operons, regulatory interactions, strain taxonomy, and sample metadata. GenomeDepot supports rapid creation of websites for user-defined genome collections that include bioinformatic tools for interactive genome browsing, Basic Local Alignment Search Tool (BLAST) search, annotation search, comparative genomic neighborhood visualization, and sequence download. Gene function annotations are generated by a customizable annotation pipeline. The pipeline runs annotation tools in Conda environments and can be easily extended with additional user-specified tools. Availability and implementation GenomeDepot is open source and distributed under the GNU General Public License via GitHub (https://github.com/aekazakov/genome-depot). GenomeDepot is implemented in Python and was tested in Ubuntu Linux. Full installation instructions and documentation are available at https://aekazakov.github.io/genome-depot/. GenomeDepot demo server is freely accessible at https://iseq.lbl.gov/demogd/.

Kazakov, Alexey [Lawrence Berkeley National Labora↗
DOE OSTI2014

DMINDA: an integrated web server for DNA motif identification and analyses

DMINDA (DNA motif identification and analyses) is an integrated web server for DNA motif identification and analyses, which is accessible at http: //csbl.bmb.uga.edu/DMINDA/. This web site is freely available to all users and there is no login requirement. This server provides a suite of cis-regulatory motif analysis functions on DNA sequences, which are important to elucidation of the mechanisms of transcriptional regulation: (i) de novo motif finding for a given set of promoter sequences along with statistical scores for the predicted motifs derived based on information extracted from a control set, (ii) scanning motif instances of a query motif in provided genomic sequences, (iii) motif comparison and clustering of identified motifs, and (iv) co-occurrence analyses of query motifs in given promoter sequences. The server is powered by a backend computer cluster with over 150 computing nodes, and is particularly useful for motif prediction and analyses in prokaryotic genomes. We believe that DMINDA, as a new and comprehensive web server for cis-regulatory motif finding and analyses, will benefit the genomic research community in general and prokaryotic genome researchers in particular.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Dimensional crossover in the quasi-one-dimensional superconductor Tl 2 Mo 6 Se 6

Here, we present magnetic penetration depth and electrical transport data in single crystals of quasi-one-dimensional (q1D) Tl 2 Mo 6 Se 6 , which reveal a 1D→3D superconducting dimensional crossover. The c-axis penetration depth shows the onset of superconducting fluctuations below T ons 1D = 6.7 K, whereas signatures of superconductivity in the ab-plane penetration depth (a uniquely sensitive probe of the transverse phase stiffness) only emerge below T ons 3D = 4.9 K. An anomalously low superfluid density persists down to ~3 K before rising steeply, in agreement with a theoretical model for crossovers in q1D superconductors. Our data analysis suggests that a sequence of pairing and phase fluctuation regimes controls the unusually broad superconducting transition. In particular, the electrical resistivity below T ons 3D is quantitatively consistent with the establishment of phase coherence through gradual binding of Josephson vortex strings to form 3D loops. This dimensional crossover within the superconducting state occurs despite the relatively large transverse hopping predicted from the band structure. Furthermore, our results have important consequences for the low-temperature normal state in Tl 2 Mo 6 Se 6 and similar q1D metals, which may retain one-dimensional behavior to lower temperatures than expected from theory.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2023

Impact-Driven Sampling Strategies for Hybrid Attack Graphs

Cyber-Physical Systems (CPSs) have a large input space, with discrete and continuous elements across multiple layers. Hybrid Attack Graph (HAG) provide a flexible and efficient approach to generate attack sequences for a CPS. Analysis and testing of large-scale HAGs are prohibitively costly. We propose a dimension reduction via property-preserving multi-layer graph sampling algorithms. Existing property-preserving graph sampling approaches generate a representative subgraph of an original large-sized graph while preserving the key properties, such as node and edge distribution, clustering coefficients, and betweenness. On the other hand, we propose impact-driven sampling strategies to transform the input data to a lower-dimensional representation while retaining key properties of the data.

Subasi, Omer↗
DOE OSTI2017

Identification of chalcone isomerase in the basal land plants reveals an ancient evolution of enzymatic cyclization activity for synthesis of flavonoids

Flavonoids ubiquitously distribute to the terrestrial plants and chalcone isomerase (CHI)- catalyzed intramolecular and stereospecific cyclization of chalcones is a committed step in the production of flavonoids. However, so far the bona fide CHIs are found only in vascular plants, and their origin and evolution remains elusive. We conducted transcriptomic and/or genomic sequence search, subsequent phylogenetic analysis, and detailed biochemical and genetic characterization to explore the potential existence of CHI proteins in the basal bryophyte liverwort species and the lycophyte Selaginella moellendorffii. We found that both liverwort and Selaginella species possess canonical CHI-fold proteins that cluster with their corresponding higher plant counterparts. Among them, some members exhibited bona fide CHI activity, which catalyze stereospecific cyclization of both 60- hydroxychalcone and 60-deoxychalcone, yielding corresponding 5-hydroxy and 5- deoxyflavanones, resembling the typical type II CHIs currently known to be ‘specific’ for legume plants. Expressing those primitive bona fide CHIs in the Arabidopsis chi mutant restores the seed coat transparent testa phenotype and the accumulation of flavonoids. These findings, in contrast to our current understanding of the evolution of enzymatic CHIs, suggest that emergence of the bona fide type II CHIs is an ancient evolution event that occurred before the divergence of liverwort lineages.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

SU-D-18C-02: Feasibility of Using a Short ASL Scan for Calibrating Cerebral Blood Flow Obtained From DSC-MRI

Purpose: This study aimed to evaluate the feasibility of using a short arterial spin labeling (ASL) scan for calibrating the dynamic susceptibility contrast- (DSC-) MRI in a group of patients with internal carotid artery stenosis. Methods: Six patients with unilateral ICA stenosis enrolled in the study on a 3T clinical MRI scanner. The ASL-cerebral blood flow (-CBF) maps were calculated by averaging different number of dynamic points (N=1-45) acquired by using a Q2TIPS sequence. For DSC perfusion analysis, arterial input function was selected to derive the relative cerebral blood flow (rCBF) map and the delay (Tmax) map. Patient-specific CF was calculated from the mean ASL- and DSC-CBF obtained from three different masks: (1)Tmax< 3s, (2)combined gray matter mask with mask 1, (3)mask 2 with large vessels removed. One CF value was created for each number of averages by using each of the three masks for calibrating the DSC-CBF map. The CF value of the largest number of averages (NL=45) was used to determine the acceptable range(< 10%, <15%, and <20%) of CF values corresponding to the minimally acceptable number of average (NS) for each patient. Results: Comparing DSC CBF maps corrected by CF values of NL (CBFL) in ACA, MCA and PCA territories, all masks resulted in smaller CBF on the ipsilateral side than the contralateral side of the MCA territory(p<.05). The values obtained from mask 1 were significantly different than the mask 3(p<.05). Using mask 3, the medium values of Ns were 4(<10%), 2(<15%) and 2(<20%), with the worst case scenario (maximum Ns) of 25, 4, and 4, respectively. Conclusion: This study found that reliable calibration of DSC-CBF can be achieved from a short pulsed ASL scan. We suggested use a mask based on the Tmax threshold, the inclusion of gray matter only and the exclusion of large vessels for performing the calibration.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

diBELLA: Distributed Long Read to Long Read Alignment

© 2019 ACM. We present a parallel algorithm and scalable implementation for genome analysis, specifically the problem of finding overlaps and alignments for data from "third generation" long read sequencers [29]. While long sequences of DNA offer enormous advantages for biological analysis and insight, current long read sequencing instruments have high error rates and therefore require different approaches to analysis than their short read counterparts. Our work focuses on an efficient distributed-memory parallelization of an accurate single-node algorithm for overlapping and aligning long reads. We achieve scalability of this irregular algorithm by addressing the competing issues of increasing parallelism, minimizing communication, constraining the memory footprint, and ensuring good load balance. The resulting application, diBELLA, is the first distributed memory overlapper and aligner specifically designed for long reads and parallel scalability. We describe and present analyses for high level design trade-offs and conduct an extensive empirical analysis that compares performance characteristics across state-of-the-art HPC systems as well as a commercial cloud architectures, highlighting the advantages of state-of-the-art network technologies.

Ellis, Marquita↗
DOE OSTI2026

CAHS: Context-Aware Homology Search

Protein homology search is foundational to bioinformatics: it supports annotation transfer, structure/function inference, and evolutionary analysis over rapidly expanding sequence repositories (e.g., UniProtKB). Profile hidden Markov models (pHMMs), as implemented in HMMER, remain the most widely trusted approach because they provide statistically calibrated E-values; however, their gap behavior is fixed once a profile is trained, despite biological evidence that insertion/deletion tolerance varies across flexible loops and intrinsically disordered regions. We present CAHS (Context-Aware Homology Search), a lightweight query-time adapter for pHMM search that incorporates learned and biologically motivated signals without changing HMMER's downstream search pipeline or its calibrated E-value reporting. Given a query sequence, CAHS computes per-residue representations from a protein language model and a disorder predictor, maps these to profile coordinates, and modulates only match-state transition rows (gap-open and gap-extension probabilities) while preserving Plan7 constraints. We comprehensively evaluate CAHS across six structurally diverse protein families and multi-domain architectures against a 570k-sequence target corpus. CAHS expands detection capability, retrieving thousands of additional remote homologs at relaxed thresholds by maintaining alignment quality through flexible regions. For multi-domain proteins, context-aware modulation resolves 94% of fragmented alignments. Crucially, CAHS preserves hit-set invariance at stringent operating points (E<10-10), demonstrating increased statistical confidence without inflating false positives. Furthermore, sharper statistical distinction between homologs and background noise during early filter stages yields up to a 3.87× acceleration in end-to-end wall-clock time on high-performance computing clusters. Overall, CAHS illustrates a practical AI-for-science design pattern: augmenting a trusted probabilistic model with query-specific learned signals to improve interpretable, reproducible inference in data-rich biology.

Bhattaram, Swethasree [Georgia Institute of Techno↗
DOE OSTI2020

Distributed Berkeley Efficient Long-Read to Long-Read Aligner and Overlapper (DiBELLA) v1.0.0

We present a parallel algorithm and scalable implementation for genome analysis, specifically the problem of finding overlaps and alignments for data from "third generation" long read sequencers. While long sequences of DNA offer enormous advantages for biological analysis and insight, current long read sequencing instruments have high error rates and therefore require different approaches to analysis than their short read counterparts. Our work focuses on an efficient distributed-memory parallelization of an accurate single-node algorithm for overlapping and aligning long reads. We achieve scalability of this irregular algorithm by addressing the competing issues of increasing parallelism, minimizing communication, constraining the memory footprint, and ensuring good load balance. The resulting application, DiBELLA, is the first distributed memory overlapper and aligner specifically designed for long reads and parallel scalability.

Ellis, Marquita↗
DOE OSTI2025

GenomeDepot v1.0

GenomeDepot is a web-based platform for annotation, management, and comparative analysis of microbial genomic sequences and associated data including ortholog families, protein domains, operons, regulatory interactions, strain taxonomy, and sample metadata. GenomeDepot supports rapid creation of web-sites for user-defined genome collections that include bioinformatic tools for interactive genome browsing, BLAST search, annotation search, comparative genomic neighborhood visualization, and sequence download. Gene function annotations are generated by a customizable annotation pipeline. The pipeline runs annotation tools in Conda environments and can be easily extended with additional user-specified tools.

Kazakov, Alexey [Lawrence Berkeley National Labora↗
DOE OSTI2022

Structural variant analysis of a cancer reference cell line sample using multiple sequencing technologies

The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples. We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy. A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity

The newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse superphylum including > 20 candidate phyla (a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known. Results Here, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of >600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Effect of fiber reinforcement on the process parameters of injection molding manufacturing process

Use of fillers with the resin is common in injection molding manufacturing technique to enhance the stiffness and strength of the manufactured components. However, the addition of fillers changes the rheological and mechanical properties of the material, required adjustments in the process parameters used for the manufacturing. The present study aims to investigate this impact of fillers on the process parameters of the injection molding manufacturing process. Neat Acrylonitrile Butadiene Styrene (ABS) and ABS reinforced with short glass fibers are used as the materials to perform the comprehensive numerical analysis including complete process sequence, namely filling, packing, cooling and warpage. Parametric studies are conducted to optimize the manufacturing process for minimal warpage (or shrinkage) in the produced part. The selected process parameters for the parametric study include cooling time, packing pressure, and mold temperature, all of which directly impact the quality of the manufactured parts. The optimal values obtained for these parameters are compared to examine the effect fiber reinforcement has on the manufacturing process.

Garg, Nikhil↗
DOE OSTI2020

Real-time structural motif searching in proteins using an inverted index strategy

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org ) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Using Bacteria to Determine Protein Kinase Specificity and Predict Target Substrates

The identification of protein kinase targets remains a significant bottleneck for our understanding of signal transduction in normal and diseased cellular states. Kinases recognize their substrates in part through sequence motifs on substrate proteins, which, to date, have most effectively been elucidated using combinatorial peptide library approaches. Here, we present and demonstrate the ProPeL method for easy and accurate discovery of kinase specificity motifs through the use of native bacterial proteomes that serve as in vivo libraries for thousands of simultaneous phosphorylation reactions. Using recombinant kinases expressed in E. coli followed by mass spectrometry, the approach accurately recapitulated the well established motif preferences of human basophilic (Protein Kinase A) and acidophilic (Casein Kinase II) kinases. These motifs, derived for PKA and CK II using only bacterial sequence data, were then further validated by utilizing them in conjunction with the scan-x software program to computationally predict known human phosphorylation sites with high confidence.

59 BASIC BIOLOGICAL SCIENCES↗