Social and scientific motivations to move beyond groups in allele frequencies: The TOPMed experience.

For the genomics community, allele frequencies within defined groups (or "strata") are useful across multiple research and clinical contexts. Benefits include allowing researchers to identify populations for replication or "look up" studies, enabling researchers to compare population-specific frequencies to validate findings, and facilitating assessment of variant pathogenicity in clinical contexts. However, there are potential concerns with stratified allele frequencies. These include potential re-identification (determining whether or not an individual participated in a given research study based on allele frequencies and individual-level genetic data), harm from associating stigmatizing variants with specific groups, potential reification of race as a biological rather than a socio-political category, and whether presenting stratified frequencies-and the downstream applications that this presentation enables-is consistent with participants' informed consents. The NHLBI Trans-Omics for Precision Medicine (TOPMed) program considered the scientific and social implications of different approaches for adding stratified frequencies to the TOPMed BRAVO (Browse All Variants Online) variant server. We recommend a novel approach of presenting ancestry-specific allele frequencies using a statistical method based upon local genetic ancestry inference. Notably, this approach does not require grouping individuals by either predominant global ancestry or race/ethnicity and, therefore, mitigates re-identification and other concerns as the mixture distribution of ancestral allele frequencies varies across the genome. Here we describe our considerations and approach, which can assist other genomics research programs facing similar issues of how to define and present stratified frequencies in publicly available variant databases.

Large-scale next generation sequencing based analysis of SLCO1B1 pharmacogenetics variants in the Saudi population.

BACKGROUND: SLCO1B1 plays an important role in mediating hepatic clearance of many different drugs including statins, angiotensin-converting enzyme inhibitors, chemotherapeutic agents and antibiotics. Several variants in SLCO1B1 have been shown to have a clinically significant impact, in relation to efficacy of these medications. This study provides a comprehensive overview of SLCO1B1 variation in Saudi individuals, one of the largest Arab populations in the Middle East. METHODS: The dataset of 11,889 (9,961 exomes and 1,928 pharmacogenetic gene panel) Saudi nationals, was used to determine the presence and frequencies of SLCO1B1 variants, as described by the Clinical Pharmacogenetic Implementation Consortium (CPIC). RESULTS: We identified 141 previously described SNPs, of which rs2306283 (50%) and rs4149056 (28%), were the most common. In addition, we observed six alleles [*15 (24.7%) followed by *20 (8.04%), *14 (5.86%), *5 (3.84%), *31 (0.21%) and *9 (0.03%)] predicted to be clinically actionable. Allele diplotype to phenotype conversion revealed 41 OATP1B1 diplotypes. We estimated the burden of rare, and novel predicted deleterious variants, resulting from 17 such alterations. CONCLUSIONS: The data we present, from one of the largest Arab cohorts studied to date, provides the most comprehensive overview of SLCO1B1 variants, and the subsequent OATP1B1 activity of this ethnic group, which thus far remains relatively underrepresented in available international genomic databases. We believe that the presented data provides a basis for further clinical investigations and the application of personalized statin drug therapy guidance in Arabs.

An Electrochemically Programmable Metasurface with Independently Controlled Metasurface Pixels at Optical Frequencies.

Metasurfaces have revolutionized optical technologies by offering powerful, compact, and versatile solutions to control light. Conducting polymers, characterized by their conjugated molecular structures, facilitate charge transport and exhibit interesting electrical, optical, and mechanical properties. Integrating conducting polymers with optical metasurfaces can unlock new opportunities and functionalities in modern optics. In this work, we demonstrate an electrochemically programmable metasurface with independently controlled metasurface pixels at optical frequencies. Electrochemical modulation of locally conjugated polyaniline on gold nanorods, which are arranged on addressable electrodes according to the Pancharatnam-Berry phase design, enables dynamic control over the metasurface pixels into programmable configurations. With the same metasurface device, we showcase diverse optical functions, including dynamic beam diffraction and varifocal lensing along and off the optical axis. The synergy between flat optics and conducting polymer science holds immense potential to enhance the performance and function versatility of metasurfaces, paving the way for innovative optical applications.

Evolution of the SARS-CoV-2 Mutational Spectrum.

SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.

Assisting the analysis of insertions and deletions using regional allele frequencies.

Accurate estimation of population allele frequency (AF) is crucial for gene discovery and genetic diagnostics. However, determining AF for frameshift-inducing small insertions and deletions (indels) faces challenges due to discrepancies in mapping and variant calling methods. Here, we propose an innovative approach to assess indel AF. We developed CRAFTS-indels (Calculating Regional Allele Frequency Targeting Small indels), an algorithm that combines AF of distinct indels within a given region and provides "regional AF" (rAF). We tested and validated CRAFTS-indels using three independent datasets: gnomAD v2 (n=125,748 samples), an internal dataset (IGM; n=39,367), and the UK BioBank (UKBB; n=469,835). By comparing rAF against standard AF, we identified rare indels with rAF exceeding standard AF (sAF≤10-4 and rAF>10-4) as "rAF-hi" indels. Notably, a high percentage of rare indels were "rAF-hi", with a higher proportion in gnomAD v2 (11-20%) and IGM (11-22%) compared to the UKBB (5-9% depending on the CRAFTS-indels' parameters). Analysis of the overlap of regions based on their rAF with low complexity regions and with ClinVar classification supported the pertinence of rAF. Using the internal dataset, we illustrated the utility of CRAFTS-indel in the analysis of de novo variants and the potential negative impact of rAF-hi indels in gene discovery. In summary, annotation of indels with cohort specific rAF can be used to handle some of the limitations of current annotation pipelines and facilitate detection of novel gene disease associations. CRAFTS-indels offers a user-friendly approach to providing rAF annotation. It can be integrated into public databases such as gnomAD, UKBB and used by ClinVar to revise indel classifications.

Exploring the Tl 2 H 2 potential energy surface: A comparative analysis with group 13 systems and experiment.

Thallium chemistry is experiencing unprecedented importance. Therefore, it is valuable to characterize some of the simplest thallium compounds. Stationary points along the singlet and triplet Tl 2 H 2 potential energy surface have been characterized. Stationary point geometries were optimized with the CCSD(T)/aug-cc-pwCVQZ-PP method. Harmonic vibrational frequencies were computed at the same level of theory while anharmonic vibrational frequencies were computed at the CCSD(T)/aug-cc-pwCVTZ-PP level of theory. Final energetics were obtained with the CCSDT(Q) method. Basis sets up to augmented quintuple-zeta cardinality (aug-cc-pwCV5Z-PP) were employed to obtain energetics in order to extrapolate to the complete basis set limits using the focal point approach. Zero-point vibrational energy corrections were appended to the extrapolated energies in order to determine relative energies at 0 K. It was found that the planar dibridged isomer lies lowest in energy while the linear structure lies highest in energy. The results were compared to other group 13 M 2 H 2 (M = B, Al, Ga, In, and Tl) theoretical studies and some interesting variations are found. With respect to experiment, incompatibilities exist.

Potential energy surfaces and dynamic properties via ab initio composite and density functional approaches.

Vibrational spectroscopy enables critical insight into the structural and dynamic properties of molecules. Presently, the majority of theoretical approaches to spectroscopy employ wavefunction-based ab initio or density functional methods that rely on the harmonic approximation. This approximation breaks down for large molecules with strongly anharmonic bonds or for molecules with large internuclear separations. An alternative to these methods involves generating molecular anharmonic potential energy surfaces (potentials) and using them to extrapolate the vibrational frequencies. This study examines the efficacy of density functional theory (DFT) and the correlation consistent Composite Approach (ccCA) in generating anharmonic frequencies from potentials of small main group molecules. Vibrational self-consistent field Theory (VSCF) and post-VSCF methods were used to calculate the fundamental frequencies of these molecules from their potentials. Functional choice, basis set selection, and mode-coupling are also examined as factors in influencing accuracy. The absolute deviations for the calculated frequencies using potentials at the ccCA level of theory were lower than the potentials at the DFT level. With DFT resulting in bending modes that are better described than those of ccCA, a multilevel DFT:ccCA approach where DFT potentials are used for single vibrational mode potentials and ccCA is used for vibrational mode-mode couplings can be utilized for larger polyatomic systems. The frequencies obtained with this multilevel approach using VCIPSI-PT2 were closer to experimental frequencies than the scaled harmonic frequencies, indicating the success of utilizing post-VSCF methods to generate more accurate representations of computed infrared spectra.

A similarity-based deep learning approach for determining the frequencies of drug side effects.

The side effects of drugs present growing concern attention in the healthcare system. Accurately identifying the side effects of drugs is very important for drug development and risk assessment. Some computational models have been developed to predict the potential side effects of drugs and provided satisfactory performance. However, most existing methods can only predict whether side effects will occur and cannot determine the frequency of side effects. Although a few existing methods can predict the frequency of drug side effects, they strongly depend on the known drug-side effect relationships. Therefore, they cannot be applied to new drugs without known side effect frequency information. In this paper, we develop a novel similarity-based deep learning method, named SDPred, for determining the frequencies of drug side effects. Compared with the existing state-of-the-art models, SDPred integrates rich features and can be applied to predict the side effect frequencies of new drugs without any known drug-side effect association or frequency information. To our knowledge, this is the first work that can predict the side effect frequencies of new drugs in the population. The comparison results indicate that SDPred is much superior to all previously reported models. In addition, some case studies also demonstrate the effectiveness of our proposed method in practical applications. The SDPred software and data are freely available at https://github.com/zhc940702/SDPred, https://zenodo.org/record/5112573 and https://hub.docker.com/r/zhc940702/sdpred.

A Diffusion-Based Approach for Simulating Forward-in-Time State-Dependent Speciation and Extinction Dynamics.

We establish a general framework using a diffusion approximation to simulate forward-in-time state counts or frequencies for cladogenetic state-dependent speciation-extinction (ClaSSE) models. We apply the framework to various two- and three-region geographic-state speciation-extinction (GeoSSE) models. We show that the species range state dynamics simulated under tree-based and diffusion-based processes are comparable. We derive a method to infer rate parameters that are compatible with given observed stationary state frequencies and obtain an analytical result to compute stationary state frequencies for a given set of rate parameters. We also describe a procedure to find the time to reach the stationary frequencies of a ClaSSE model using our diffusion-based approach, which we demonstrate using a worked example for a two-region GeoSSE model. Finally, we discuss how the diffusion framework can be applied to formalize relationships between evolutionary patterns and processes under state-dependent diversification scenarios.

Genetic profile of RHCE, Kell, Duffy, Kidd, Diego and MNS hybrid glycophorins blood groups in ethnic northeastern Thais: Alleles, genotypes and risk of alloimmunisation.

BACKGROUND: Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn (HDFN). This study aimed to determine the frequencies of alleles, genotypes, and risk of alloimmunisation of clinically significant blood group systems in ethnic northeastern Thais. METHODS: In total, 345 unrelated, healthy, ethnic northeastern Thais were tested using the in-house PCR-sequence specific primers (PCR-SSP) method for simultaneously genotyping of RHCE, Kell, Duffy, Kidd, Diego and MNS glycophorin hybrids and results confirmed by Sanger sequencing. RESULTS: In this cohort, the alleles RHCE*C (81.0%) and RHCE*e (84.8%) were more prevalent than RHCE*c (19.0%) and RHCE*E (15.2%). The most common predicted haplotype combinations of the RHCE alleles were C+c-E-e+(R1R1) (59.4%) followed by the C+c+E+e+ (R1R2) (20.6%) and C+c+E-e+ (R1r) (11.3%). The KEL*01 allele was not found in this study. The frequencies of FY*01 and FY*02 were 88.3% and 11.7%, respectively. The genotype FY*02/02 was found in four samples (1.2%). The frequencies of JK*01 and JK*02 were 52.5% and 47.5%, respectively. Homozygous JK*02/02 was found in 81 samples (23.5%). The frequencies of DI*01 and DI*02 were 0.6% and 99.4%, respectively. In total, 64 samples (18.6%) were found to carry the MNS glycophorin hybrids. CONCLUSIONS: Our results indicated a possible high risk of c, E, Fyb, Jka, Jkb and Mia alloimmunisation in these populations. Moreover, methods established for genotyping clinically significant blood groups in this study can now be utilised in routine clinical application.

Pharmacogenomics and adverse effects of anti-infective drugs in children.

Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.

HLA Polymorphisms and Clinical Manifestations in IgA Vasculitis.

Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study. Genomic DNA was extracted from whole peripheral blood, and HLA-A, -B, -DRB1 and -DQB1 gene polymorphism analysis was performed. HLA-A*03 (21.4% vs. 12.38%, p = 0.0092), HLA-B*37 (2.9% vs. 0.2%, p = 0.0054) and HLA-DRB1*12 (3.1% vs. 0.7%, p = 0.0216) alleles were significantly more frequent in IgAV patients than in controls. High-resolution typing revealed significantly higher frequency of HLA-DRB1*10:01 and -DRB1*11:03 among IgAV patients with gastrointestinal manifestations of the disease in comparison to controls (p = 0.0021 and p = 0.0301, respectively), while HLA-DRB1*14:01P occurred significantly more often in the group of patients who developed nephritis during the course of the disease (17.5% vs. 4.5%, p = 0.0006). Our results demonstrated that there is an association of HLA-A*03, HLA-B*37 and HLA-DRB1*12 alleles with susceptibility to IgAV in the examined Croatian pediatric population. Studies which aim to determine the HLA profile may contribute to the elucidation of the genetic background of autoimmune diseases, including IgAV.

Systematic Study of Different Types of Interactions in α-, ß- and γ-Cyclodextrin: Quantum Chemical Investigation.

In this work, comprehensive ab initio quantum chemical calculations using the DFT level of theory were performed to characterize the stabilization interactions (H-bonding and hyperconjugation effects) of two stable symmetrical conformations of α-, ß-, and γ-cyclodextrins (CDs). For this purpose, we analyzed the electron density using "Atom in molecules" (AIM), "Natural Bond Orbital" (NBO), and energy decomposition method (CECA) in 3D and in Hilbert space. We also calculated the H-bond lengths and OH vibrational frequencies. In every investigated CD, the quantum chemical descriptors characterizing the strength of the interactions between the H-bonds of the primary OH (or hydroxymethyl) and secondary OH groups are examined by comparing the same quantity calculated for ethylene glycol, α-d-glucose (α-d-Glcp) and a water cluster as reference systems. By using these external standards, we can characterize more quantitatively the properties of these bonds (e.g., strength). We have demonstrated that bond critical points (BCP) of intra-unit H-bonds are absent in cyclodextrins, similar to α-d-Glcp and ethylene glycol. In contrast, the CECA analysis showed the existence of an exchange (bond-like) interaction between the interacting O…H atoms. Consequently, the exchange interaction refers to a chemical bond, namely the H-bond between two atoms, unlike BCP, which is not suitable for its detection.

A joint analysis of accessibility and household trip frequencies by travel mode.

This paper examines the endogenous relationship between residential level of accessibility and household trip frequencies to tease out the direct and indirect effects of observed behavioural differences. We estimate a multivariate ordered probit model system, which allows dependence in both observed and unobserved factors, using data from the 2016 Transportation Tomorrow Survey (TTS), a household travel survey in the Greater Golden Horseshoe Area (GGH) in Toronto. The modelling framework is used to analyse the influence of exogenous variables on eight outcome variables of accessibility levels and trip frequencies by four modes (auto, transit, bicycle and walk), and to explore the nature of the relationships between them. The results confirm our hypothesis that not only does a strong correlation exist between the residential level of accessibility and household trip frequency, but there are also direct effects to be observed. The complementarity effect between auto accessibility and transit trips, and the substitution effect observed between transit accessibility and auto trips highlight the residential neighbourhood dissonance of transit riders. It shows that locations with better transit service are not necessarily locations where people who make more transit trips reside. Essentially, both jointness (due to error correlations) as well as directional effects observed between accessibility and trip frequencies of multiple modes offer strong support for the notion that accessibility and trip frequency by mode constitute a bundled choice and need to be considered as such.

Genetic diversity of SNPs associated with candidate genes for heat stress in Coreño Creole cattle in Mexico.

Mexican Coreño Creole cattle are an important genetic resource adapted to local environmental conditions, so the study of their genetic diversity is essential to know their status and implement conservation programs and their use for crossbreeding. This study evaluated the genetic diversity of heat stress tolerance characteristics of Coreño Creole cattle, and a gene ontology enrichment was performed to know the biological processes in which candidate genes are involved. A total of 48 samples from three localities of Nayarit were genotyped using 777 K Illumina BovineHD BeadChip and 34 single nucleotide polymorphisms associated with candidate genes were selected. Genetic diversity was analyzed using allelic frequencies, expected heterozygosity (He), and Wright's fixation index (FST) using PLINK v1.9 software. Candidate genes were uploaded to the open-source GOnet for pathway analysis and linkage to biological processes. Coreño Creole cattle showed low genetic diversity (He = 0.35), the average FST obtained was 0.044, and only eight markers had allele frequencies higher than 0.80 in the three locations. We found that the genes GOT1 and NCAD are related in the biological processes of stress response, cell differentiation, and homeostatic process. The results revealed that Coreño Creole cattle have low genetic diversity; this could be due to the isolation of these populations.

Non-random Codon Usage of Synonymous and Non-synonymous Mutations in the Human HLA-A Gene.

The structure and function of human leucocyte antigen (HLA-A) is well known and is an extremely variable protein. From the public HLA-A database, we chose 26 high frequency HLA-A alleles (45% of sequenced alleles). Using five arbitrary references from these alleles, we analyzed synonymous mutations at the third codon position (sSNP3) and non-synonymous mutations (NSM). Both mutation types showed non-random locations of 29 sSNP3 codons and 71 NSM codons in the five reference lists. Most sSNP3 codons show identical mutation types with many mutations resulting from cytosine deamination. We proposed 23 ancestral parents of sSNP3 in five reference sequences using conserved parents in five unidirectional codons and 18 majority parents in reciprocal codons. These 23 proposed ancestral parents show exclusive codon usage of G3 or C3 parents located on both DNA strands that mutate to A3 or T3 variants mostly (76%) by cytosine deamination The sSNP3 and NSM show clear separation of the two variant types with most sSNP3 located in conserved areas in exons 2, 3 and 4, compared to most NSM appearing in two Variable Areas with no sSNP3 in the latter parts of exons 2 (α1) and 3 (α2). The Variable Areas contain NSM (polymorphic) residues at the center of the groove that bind the foreign peptide. We find distinctly different mutation patterns in NSM codons from those of sSNP3. Namely, G-C to A-T mutation frequency was much smaller, suggesting that evolutional pressures of deamination and other mechanisms applied to the two areas are significantly different.

Thermal Plasticity in Behavioral Traits Mediates Mating and Reproductive Dynamics in an Ectotherm.

AbstractEnvironmental temperatures potentially influence reproductive performance and sexual selection by restricting opportunities for activity. However, explicit tests of the behavioral mechanisms linking thermal variation to mating and reproductive performance are rare. We address this gap in a temperate lizard by combining social network analysis with molecular pedigree reconstruction in a large-scale thermal manipulation experiment. Populations exposed to cool thermal regimes presented fewer high-activity days compared with populations exposed to a warmer regime. While plasticity in thermal activity responses in males masked overall differences in activity levels, prolonged restriction nevertheless affected the timing and consistency of male-female interactions. Females were less capable than males of compensating for lost activity time under cold stress, and less active females in this group were significantly less likely to reproduce. While sex-biased activity suppression appeared to limit male mating rates, this did not correspond to a heightened intensity of sexual selection or shifts in the targets of sexual selection. In many populations facing thermal activity restriction, sexual selection on males may play a limited role relative to other thermal performance traits in facilitating adaptation.

Accurate thermochemistry at affordable cost by means of an improved version of the JunChS-F12 model chemistry.

The junChS-F12 composite method has been improved by means of the latest implementation of the CCSD(F12*)(T+) ansatz and validated for the thermochemistry of molecules containing atoms of the first three rows of the periodic table. A thorough benchmark showed that this model, in conjunction with cost-effective revDSD-PBEP86-D3(BJ) reference geometries, offers an optimal compromise between accuracy and computational cost. If improved geometries are sought, the most effective option is to add MP2-F12 core-valence correlation corrections to CCSD(T)-F12b/jun-cc-pVTZ geometries without the need of performing any extrapolation to the complete basis set limit. In the same vein, CCSD(T)-F12b/jun-cc-pVTZ harmonic frequencies are remarkably accurate without any additional contribution. Pilot applications to noncovalent intermolecular interactions, conformational landscapes, and tautomeric equilibria confirm the effectiveness and reliability of the model.

Gas-phase thermochemistry of noncovalent ligand-alkali metal ion clusters: An impact of low frequencies.

The experimental gas-phase thermochemistry of reactions: M+ (S)n-1 + S → M+ (S)n and M+ + nS→ M+ (S)n , where M is an alkali metal and S is acetonitrile/ammonia, is reproduced. Three approximations are tested: (1) scaled rigid-rotor-harmonic-oscillator (sRRHO); (2) the sRRHO(100) identical to (1), but with all vibrational frequencies smaller than 100 cm-1 replaced with 100 cm-1 ; (3) Grimme's modified scaled RRHO (msRRHO) (Grimme, Chem. Eur. J., 2012, 18, 9955-9964). The msRRHO approach provides the most accurate reaction entropies with the mean unsigned error (MUE) below 5.5 cal mol-1 K-1 followed by sRRHO(100) and sRRHO with MUEs of 7.2 and 16.9 cal mol-1 K-1 . For the first time, we propose using the msRRHO scheme to calculate the enthalpy contribution that is further utilized to arrive at reaction Gibbs free energies (∆Gr ) ensuring the internal consistency. The final ∆Gr MUEs for msRRHO, sRRHO(100) and sRRHO schemes are 1.2, 3.6 and 3.1 kcal mol-1 .

A novel graph attention model for predicting frequencies of drug-side effects from multi-view data.

Identifying the frequencies of the drug-side effects is a very important issue in pharmacological studies and drug risk-benefit. However, designing clinical trials to determine the frequencies is usually time consuming and expensive, and most existing methods can only predict the drug-side effect existence or associations, not their frequencies. Inspired by the recent progress of graph neural networks in the recommended system, we develop a novel prediction model for drug-side effect frequencies, using a graph attention network to integrate three different types of features, including the similarity information, known drug-side effect frequency information and word embeddings. In comparison, the few available studies focusing on frequency prediction use only the known drug-side effect frequency scores. One novel approach used in this work first decomposes the feature types in drug-side effect graph to extract different view representation vectors based on three different type features, and then recombines these latent view vectors automatically to obtain unified embeddings for prediction. The proposed method demonstrates high effectiveness in 10-fold cross-validation. The computational results show that the proposed method achieves the best performance in the benchmark dataset, outperforming the state-of-the-art matrix decomposition model. In addition, some ablation experiments and visual analyses are also supplied to illustrate the usefulness of our method for the prediction of the drug-side effect frequencies. The codes of MGPred are available at https://github.com/zhc940702/MGPred and https://zenodo.org/record/4449613.