SPARC Software Research Articles

Hybrid assembly of ultra-long Nanopore reads augmented with 10x-Genomics contigs: Demonstrated with a human genome

The 3rd generation of sequencing (3GS) technologies generate ultra-long reads (up to 1 Mb), which makes it possible to eliminate gaps and effectively resolve repeats in genome assembly. However, the 3GS technologies suffer from the high base-level error rates (15%–40%) and high sequencing costs. To address these issues, the hybrid assembly strategy, which utilizes both 3GS reads and inexpensive NGS (next generation sequencing) short reads, was invented. Here, we use 10×-Genomics® technology, which integrates a novel bar-coding strategy with Illumina® NGS with an advantage of revealing long-range sequence information, to replace common NGS short reads for hybrid assembly of long erroneous 3GS reads. We demonstrate the feasibility of integrating the 3GS with 10×-Genomics technologies for a new strategy of hybrid de novo genome assembly by utilizing DBG2OLC and Sparc software packages, previously developed by the authors for regular hybrid assembly. Using a human genome as an example, we show that with only 7× coverage of ultra-long Nanopore® reads, augmented with 10× reads, our approach achieved nearly the same level of quality, compared with non-hybrid assembly with 35× coverage of Nanopore reads. Compared with the assembly with 10×-Genomics reads alone, our assembly is gapless with slightly high cost. These results suggest that our new hybrid assembly with ultra-long 3GS reads augmented with 10×-Genomics reads offers a low-cost (less than ¼ the cost of the non-hybrid assembly) and computationally light-weighted (only took 109 calendar hours with peak memory-usage = 61GB on a dual-CPU office workstation) solution for extending the wide applications of the 3GS technologies.

Aqueous phase hydration and hydrate acidity of perfluoroalkyl and n:2 fluorotelomer aldehydes

ABSTRACTThe SPARC software program and comparative density functional theory (DFT) calculations were used to investigate the aqueous phase hydration equilibrium constants (Khyd) of perfluoroalkyl aldehydes (PFAlds) and n:2 fluorotelomer aldehydes (FTAlds). Both classes are degradation products of known industrial compounds and environmental contaminants such as fluorotelomer alcohols, iodides, acrylates, phosphate esters, and other derivatives, as well as hydrofluorocarbons and hydrochlorofluorocarbons. Prior studies have generally failed to consider the hydration, and subsequent potential hydrate acidity, of these compounds, resulting in incomplete and erroneous predictions as to their environmental behavior. In the current work, DFT calculations suggest that all PFAlds will be dominantly present as the hydrated form in aqueous solution. Both SPARC and DFT calculations suggest that FTAlds will not likely be substantially hydrated in aquatic systems or in vivo. PFAld hydrates are expected to have pKa values in the range of phenols (ca. 9 to 10), whereas n:2 FTAld hydrates are expected to have pKa values ca. 2 to 3 units higher (ca. 12 to 13). In order to avoid spurious modeling predictions and a fundamental misunderstanding of their fate, the molecular and/or dissociated hydrate forms of PFAlds and FTAlds need to be explicitly considered in environmental, toxicological, and waste treatment investigations. The results of the current study will facilitate a more complete examination of the environmental fate of PFAlds and FTAlds.

Use of the SPARC software program to calculate hydrolysis rate constants for the polymeric brominated flame retardants BC-58 and FR-1025

ABSTRACTThe SPARC software program was used to estimate the acid-catalyzed, neutral, and base-catalyzed hydrolysis rate constants for the polymeric brominated flame retardants BC-58 and FR-1025. Relatively rapid hydrolysis of BC-58, producing 2,4,6-tribromophenol—and ultimately tetrabromobisphenol A—as the hydrolytically stable end products from all potential hydrolysis reactions, is expected in both environmental and biological systems with starting material hydrolytic half-lives (t1/2,hydr) ranging from less than 1 h in marine systems, several hours in cellular environments, and up to several weeks in slightly acid fresh waters. Hydrolysis of FR-1025 to give 2,3,4,5,6-pentabromobenzyl alcohol is expected to be slower (t1/2,hydr less than 0.5 years in marine systems up to several years in fresh waters) than BC-58, but is also expected to occur at rates that will contribute significantly to environmental and in vivo loadings of this compound.

Assessment of atmospheric distribution of polycyclic aromatic hydrocarbons using a molecular structure model

In this paper, a comparison of experimentally obtained and SPARC software v4.6 modelled values of gas/particle partitioning coefficients was conducted to determine whether the evaluation of atmospheric distribution of PAH molecules can be performed using a molecular structure model. Partitioning coefficients were calculated for sixteen EPA PAHs, in thirty-nine samples of ambient air collected at nineteen urban, industrial, highly contaminated and background sites in the Republic of Serbia and Bosnia and Herzegovina. For obtaining samples of ambient air, the conventional high volume (Hi-Vol) methodology was applied, whereby gaseous and particulate phase data collection was conducted simultaneously by glass fibre filters (GFFs) and polyurethane foam filters (PUFs). The best prediction was for PAHs with 5 or more rings (benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, indeno(1,2,3-cd)perylene and benzo(ghi)perylene). For evaluating the applicability of SPARC software predictions of gas/particle partitioning coefficients for the existing conditions, the results were compared with those obtained by applying other frequently used and highly ranked theoretical models of phase distributions, namely Junge–Pankow adsorption model, KOA absorption model, Dachs–Eisenreich dual model and PP-LFER model.

Benchmarking the SPARC software program for estimating solubilities of naphthalene and anthracene in organic solvents

AbstractThe SPARC software program was benchmarked for calculating the solubilities of two representative polyaromatic hydrocarbons (PAHs), naphthalene and anthracene, in a range of organic solvents at various temperatures. Although SPARC was able to reasonably approximate the solubilities of naphthalene in some organic solvents, gross errors were obtained for other solvents. For anthracene, poor prediction performance was observed in all solvents considered. Overall, the results suggest that SPARC is currently not suitable for accurately predicting the solubilities of representative PAHs relevant for the petroleum sector in various organic solvents.

Benchmarking the SPARC software program for estimating solubilities of naphthalene and anthracene in organic solvents

Benchmarking the SPARC software program for estimating solubilities of naphthalene and anthracene in organic solvents

Dow and Kaw,eff vs. Kow and K°aw: Acid/base ionization effects on partitioning properties and screening commercial chemicals for long-range transport and bioaccumulation potential

A set of 543 ionizable commercial organic compounds with various acid/base functionalities and experimental octanol-water partitioning coefficients (log Kow) were obtained from the Canadian Domestic Substances List. Corresponding pH-dependent octanol-water distribution coefficients (log Dow) and air-water partitioning coeffients (log Kaw,eff) were estimated using the SPARC software program, as were log Kow and log K°aw values for the neutral forms of each chemical. Significant ionization dependent effects on chemical screening results at various pH values were obtained using established criteria for bioaccumulation potential (BAP) in aquatic organisms, terrestrial animals, and humans, as well as for atmospheric long range transport potential (LRTP). Future modelling efforts for environmental and toxicological screening of commercial chemicals should therefore explicitly include the influence of ionization for both weak and strong organic acids and bases on bioavailability and air-water mobility within the respective regulatory frameworks. Functional group specific sorption of both ionizable and neutral compounds to particulate and dissolved inorganic and organic matter will also affect chemical screening results for BAP and LRTP. More complex sorption related modelling in various types of representative aquatic systems also appears necessary to achieve reliable chemical screening results for commercial organic compounds.

PKa values of the monohydroxylated polychlorinated biphenyls (OH-PCBs), polybrominated biphenyls (OH-PBBs), polychlorinated diphenyl ethers (OH-PCDEs), and polybrominated diphenyl ethers (OH-PBDEs)

The SPARC software program aqueous pKa prediction module was validated against corresponding experimental acidity constants for chlorinated and brominated phenols and the limited experimental aqueous pKa data sets for monohydroxylated polychlorinated biphenyls (OH-PCBs), polychlorinated diphenyl ethers (OH-PCDEs), and polybrominated diphenyl ethers (OH-PBDEs). pKa values were then estimated for all 837 monohydroxylated mono- through nona-halogenated congeners in each of the OH-PCB, OH-PCDE, and OH-PBDE classes, as well as for the monohydroxylated polybrominated biphenyls (OH-PBBs), giving a total of 3348 compounds. Large intrahomolog pKa variation by up to six units is expected within each contaminant class, with pKa values ranging from about 4 to 11 dependent on the degree and pattern of halogenation. Increasing halogenation generally decreased the average pKa within each homolog group. Significant intrahomolog differences in pKa values exist between OH-PCB, OH-PBB, OH-PCDE, and OH-PBDE congeners, including large acidity constant variation between isomers with equivalent halogenation patterns but varying location of the hydroxy moiety. Congener specific pH dependent investigations into the partitioning and degradation behaviors of these compounds are necessary, including greater consideration of analyte ionization effects during their extraction and analysis.

Aqueous phase hydration and hydrate acidity of perfluoroalkyl and n:2 fluorotelomer aldehydes

AbstractPerfluoroalkyl aldehydes (PFAlds) and n:2 fluorotelomer aldehydes (FTAlds) are degradation products of precursor compounds that include fluorotelomer alcohols, iodides, acrylates, phosphate esters, and other derivatives, as well as hydrofluorocarbons and hydrochlorofluorocarbons. The SPARC software program and comparative density functional theory (DFT) calculations were used to investigate the aqueous phase hydration equilibrium constants (K~hyd~) of PFAlds and FTAlds. DFT studies suggest that all PFAlds will be dominantly present as the hydrated form in aqueous solution. While SPARC correctly estimates the K~hyd~ for the C~1~ PFAld, it appears to incorrectly predict a large decline in K~hyd~ (particularly between C~1~ and C~2~) with increasing perfluoroalkyl chain length for this class of compounds. Both SPARC and DFT investigations suggest that FTAlds will not likely be substantially hydrated in aquatic systems or in vivo. Using corrected SPARC estimates, PFAld hydrates are expected to have pK~a~ values in the range of phenols (ca. 9 to 10), whereas n:2 FTAld hydrates are expected to have pK~a~ values ca. 2 to 3 units higher (ca. 12 to 13). Where relevant, the molecular and/or dissociated hydrate forms of PFAlds and FTAlds need to be explicitly considered in environmental, toxicological, and waste treatment investigations.

Modeling the hydrolysis of the polymeric brominated flame retardants BC-58 and FR-1025

AbstractThe SPARC software program was used to estimate the acid-catalyzed, neutral, and base-catalyzed hydrolysis rate constants for the polymeric brominated flame retardants BC-58 and FR-1025, as well as the hydrolyzable daughter products of BC-58. Relatively rapid hydrolysis of BC-58, producing 2,4,6-tribromophenol and tetrabromobisphenol A as the hydrolytically stable end products from all potential hydrolysis reactions, is expected in both environmental and biological systems with starting material hydrolytic half lives (t~1/2,hydr~) ranging from less than one hour in marine systems, several hours in cellular environments, and up to several weeks in slightly acid fresh waters. Hydrolysis of FR-1025 to give 2,3,4,5,6-pentabromobenzyl alcohol is expected to be slower (t~1/2,hydr~ less than 0.5 years in marine systems up to several years in fresh waters) than BC-58, but is also expected to occur at rates that will contribute significantly to environmental and in vivo loadings of this compound.

A new class of perfluorinated acid contaminants: Primary and secondary substituted perfluoroalkyl sulfonamides are acidic at environmentally and toxicologically relevant pH values

The SPARC software program was validated for nitrogen-hydrogen acidity constant estimation of primary and secondary sulfonamides against a broad suite of substituted derivatives with experimental datasets in water and dimethylsulfoxide solvent systems and across a wide pKa range. Following validation, amidic proton pKa values were estimated for all C1 through C8 congeners of five major perfluoroalkyl sulfonamide classes: unsubstituted sulfonamides, N-methyl and N-ethyl sulfonamides, sulfonamidoethanols, and sulfonamidoacetates. Branching of the perfluoroalkyl chain is expected to have substantial impacts on amide moiety acidity in these contaminant groups, with intrahomologue variability of up to four pKa units and increasing pKa values with both increasing chain branching and greater proximity of the chain branching to the sulfonamide head group. Perfluoroalkyl chain length is not predicted to have a substantial influence on sulfonamide acidity. The predicted pKa values and variability are anticipated to have substantial impacts on the environmental partitioning and degradation of these compounds, as well as the modes and magnitudes of toxicological effects. Substantial pH dependent isomeric fractionation of perfluoroalkyl sulfonamides is expected both in situ and in vivo, necessitating the incorporation of amide group acidities in multimedia environmental models and pharmacokinetic studies.

Estimated congener specific gas-phase atmospheric behavior and fractionation of perfluoroalkyl compounds: Rates of reaction with atmospheric oxidants, air-water partitioning, and wet/dry deposition lifetimes

A quantitative structure-activity model has been validated for estimating congener specific gas-phase hydroxyl radical reaction rates for perfluoroalkyl sulfonic acids (PFSAs), carboxylic acids (PFCAs), aldehydes (PFAls) and dihydrates, fluorotelomer olefins (FTOls), alcohols (FTOHs), aldehydes (FTAls), and acids (FTAcs), and sulfonamides (SAs), sulfonamidoethanols (SEs), and sulfonamido carboxylic acids (SAAs), and their alkylated derivatives based on calculated semi-empirical PM6 method ionization potentials. Corresponding gas-phase reaction rates with nitrate radicals and ozone have also been estimated using the computationally derived ionization potentials. Henry's law constants for these classes of perfluorinated compounds also appear to be reasonably approximated by the SPARC software program, thereby allowing estimation of wet and dry atmospheric deposition rates. Both congener specific gas-phase atmospheric and air-water interface fractionation of these compounds is expected, complicating current source apportionment perspectives and necessitating integration of such differential partitioning influences into future multimedia models. The findings will allow development and refinement of more accurate and detailed local through global scale atmospheric models for the atmospheric fate of perfluoroalkyl compounds.

Examining the PM6 semiempirical method for pKa prediction across a wide range of oxyacids

AbstractThe pK~a~ estimation ability of the semiempirical PM6 method was evaluated across a broad range of oxyacids and compared to results obtained using the SPARC software program. Compound classes under consideration included acetic acids, alicyclic and aromatic heterocyclic acids, benzoic acids, boronic acids, hydroxamic acids, oximes, peroxides, peroxyacids, phenols, α-saturated acids, α-saturated alcohols, sulfinic acids, α-unsaturated acids, and α-unsaturated alcohols. PM6 accurately predicts the acidity of acetic and benzoic acids and their derivatives, but is less reliable for alicyclic and aromatic heterocyclic acids and phenols. α-Saturated acids are reliably modeled by PM6 except for polyacid derivatives with α-alcohol moieties. α-Saturated alcohols only appear to yield reliable PM6 results where an α-hydroxy or α-alkoxy moiety is absent. Carboxylic acids with simple α-alkene unsaturation are well approximated by PM6 except where alkyne α-unsaturation or α-carboxylation are also present. The PM6 and SPARC methods exhibit approximately equal pKa prediction performance for the acetic, alicyclic, and benzoic acids. SPARC outperforms PM6 on the peroxides, peroxyacids, phenols, and α-saturated acids and α-saturated alcohols. pKa values for boron, nitrogen, and sulfur oxyacids do not appear to be reliably estimated by either the PM6 or SPARC methods. The findings will help guide the potential appropriateness of results from the PM6 pK~a~ estimation method for waste treatment and environmental fate investigations.