Protein-coding Genes Research Articles

The T2T Genome of the Domesticated Silkworm Bombyx mori

Genome sequences contain the fundamental genetic information that largely determines the biology of a species. Over the past 20 years, advancements in high-throughput sequencing technologies and bioinformatics tools have matured, facilitating genome assembly and ushering in the telomere-to-telomere (T2T) era. Bombyx mori is renowned as a silk-producing insect and serves as an important model organism extensively studied across various fields of biology. In this study, we present the first assembled T2T genome by integrating HiFi, ultra-long ONT, NGS, and Hi-C data. This assembly comprises 450,267,439 base pairs from 28 chromosomes and includes annotations for a total of 18,253 protein-coding genes. A completeness evaluation revealed that 99.1% of conserved single-copy genes were included, as determined by a BUSCO analysis. Furthermore, the consensus quality (QV) assessed through Merqury was recorded at 59.88. The proportion of repeat sequence achieved 60.77%, marking it as the highest reported value for B. mori to date. In comparison to previously published genomes, our assembly offers a more complete and higher quality representation, particularly concerning highly homologous tandem regions such as telomeres, rDNA clusters, and Gr family regions. Furthermore, our extensive experience in genome assembly, including sample preparation experience and assembly strategies to reduce complexity, will provide valuable references for other species aiming to achieve their own T2T genome assemblies.

The genome of the cryopelagic Antarctic bald notothen, Trematomus borchgrevinki.

The Antarctic bald notothen, Trematomus borchgrevinki (family Nototheniidae) occupies a high latitude, ice-laden environment and represents an extreme example of cold-specialization among fishes. We present the first, high quality, chromosome-scale genome of a female T. borchgrevinki individual comprised of 23 putative chromosomes, the largest of which is 65 megabasepairs (Mbp) in length. The total length of the genome 935.13 Mbp, composed of 2,094 scaffolds, with a scaffold N50 of 42.67 Mbp. Annotation yielded 22,192 protein coding genes while 54.75% of the genome was occupied by repetitive elements; an analysis of repeats demonstrated that an expansion occurred in recent time. Conserved synteny analysis revealed that the genome architecture of T. borchgrevinki is largely maintained with other members of the notothenioid clade, although several significant translocations and inversions are present, including the fusion of orthologous chromosomes 8 and 11 into a single element. This genome will serve as a cold-specialized model for comparisons to other members of the notothenioid adaptive radiation.

Whether niche changes promote the evolution of species: a case study of Paeonia in Asia and North America

Ecological changes have been observed to promote rates of lineage diversification, yet the precise roles of ecological factors, species evolution, and environmental variability in driving species diversity remain research hot spots. The association between ecological change and lineage diversification, particularly with regard to the size of the time scale, remains poorly understood. To explore whether ecological change facilitates species evolution, we focused on the unique family Paeoniaceae, which encompasses both herbaceous and woody taxa, to investigate the evolutionary rates. As a unique family characterized by a single genus of angiosperms and comprising various climatic types, the ecological niche changes of Paeoniaceae are closely associated with the evolution, making it an ideal model for conducting association analysis. In this study, we integrated the molecular fragments and ecological factors to explore the relationship between species evolution and niche changes in Paeoniaceae. The phylogenetic tree revealed that Paeoniaceae forms a sister relationship with Penthoraceae, Haloragidaceae, Iteaceae, Crassulaceae, and Saxifragaceae, constituting an independent clade based on the positive selection of molecular fragments including two protein-coding genes and eight non-coding regions. The divergence time was estimated to be between 102 and 116 Mya (Million years ago). The phylogenetic tree within Paeonia revealed a clear division into three groups: sections of Paeonia, Moutan, and Onaepia with high support values for each branch based on the ten positive selection of molecular fragments. The rapid rate of evolution observed in Paeonia, about 0-5 Mya. In addition, ecological niche modeling showed that the potential distributions for Paeonia expanded from middle Asia to eastern Asia, and from central North America to the Northern part of North America during the Last Glacial Maximum (LGM) to Mid Holocene (MID) period. This suggests that Paeonia continuously adapted to changing ecological environments over time. Compared to the rate of climatic niche divergence and lineage diversification, the ecological niche of Paeonia underwent significant changes during the period of 3-11 Mya, occurring 5 Mya earlier than the period of evolutionary rate change. These findings offer comprehensive insights into the relationship between niche change and the evolution of species, providing valuable perspectives for further ecological cultivation efforts.

High-quality genome assembly and annotation of the crested gecko (Correlophus ciliatus).

Correlophus ciliatus, or the crested gecko, is widely kept as a pet in many countries around the world due to its ease to care and bred and its high survival rate. However, there is limited number of genomic studies on the crested gecko. In this study, we generated a high-quality chromosome-level genome assembly of the crested gecko by combining Nanopore, Illumina, and Hi-C data. The genome assemble has a size of 1.66 Gb, with scaffold N50 of 109.97 Mb, and 99.52% of the scaffold anchored on 19 chromosomes. The BUSCO analysis indicated a gene completeness of 90.3% (n=7,480), including 6,673 (89.2%) single-copy genes and 84 (1.1%) duplicated genes. Additionally, we identified 21,065 protein-coding genes using the MAKER3 annotation toolkit, with 41.98% (697.51 Mb) consisting of repetitive elements. Among these, 21,037 genes were validated through InterProScan5. Our study is the first to report a chromosome-level genome for the crested gecko. It provides valuable genomic resources for understanding molecular mechanisms under many interesting traits of the species.

Chromosome-level genome assembly of the smallscale yellowfin (Plagiognathops microlepis).

The small-scale yellowfin (Plagiognathops microlepis) is a highly valued species in East Asian aquaculture due to its adaptability and high yield. However, the lack of genomic data has impeded genetic research and breeding efforts. In this study, we utilize PacBio Hifi long-read sequencing and Hi-C technologies to construct a highly detailed genome of P. microlepis at the chromosomal level. The assembly encompasses 976.41 Mb, with an exceptional 99.84% distribution across 24 chromosomes. Notably, the contig N50 was 34.41 Mb and scaffold N50 was 38.38 Mb. The completeness of the P. microlepis genome assembly is underscored by a BUSCO score of 98.08%. A total of 25,389 protein-coding genes were identified, with a BUSCO score of 96.98%, and 99.85% of these genes were functionally annotated. Synteny relationships at the chromosome level with Danio rerio and Chanodichthys erythropterus genomes uncover small-scale chromosomal rearrangements. This high-fidelity genome assembly serves as a pivotal resource for forthcoming endeavors such as the genome structure, functional elements, comparative genomics, and evolutionary characteristics of P. microlepis and its relative species.

Investigation of Association Between Expression of DYX1C1, KIAA0319, and ROBO1 Genes and Specific Learning Disorder in Children and Adolescents.

Specific learning disorder (SLD) is prevalent worldwide and is a complex disorder with variable symptoms and significant differences among individuals. Epigenetic markers may alter susceptibility to neurodevelopmental disorders (NDDs). Aberrant expression of protein-coding (mRNA) genes in this pathology shows that the detection of epigenetic molecular biomarkers is of increasing importance in the diagnosis and treatment of individuals with SLD. We compared gene expression level of dyslexia susceptibility 1 candidate gene 1 (DYX1C1), dyslexia-associated protein KIAA0319 (KIAA0319), and roundabout guidance receptor 1 (ROBO1) between children with SLD and healthy children by performing quantitative polymerase chain reaction (qPCR). In addition, we evaluated these gene expressions of severe children with SLD compared to non-severe and male SLD children compared to females. The expression of the DYX1C1, KIAA0319, and ROBO1 genes was statistically significantly upregulated in children with SLD (P < 0.05*). DYX1C1 was also upregulated in severe SLD children (P = 0.03*). In addition, KIAA0319 and ROBO1 genes were differentially expressed in male SLD children compared to females (P < 0.05*). Furthermore, we found that DYX1C1 and ROBO1 genes significantly affect the likelihood of the SLD (respectively, P < 0.001** and P = 0.007*). We expect that the findings provided from this study may contribute to the determination expression level of the relevant genes in the diagnosis, prognosis, and treatment of SLD. In addition, our findings could be a guide for future epigenetics studies on the use of the DYX1C1, KIAA0319, and ROBO1 in therapeutic applications in the SLD.

The chloroplast genome of Cephalanthera nanchuanica (Orchidaceae): comparative and phylogenetic analysis with other Neottieae species.

Cephalanthera nanchuanica is a terrestrial orchid species and has been red listed as a second-grade protected plant due to its limited distributions in China. Initially classified within a monotypicgenus Tangtsinia, this species was later reassigned to Cephalanthera based on morphological and molecular data. However, previous phylogenetic analyses of Cephalanthera using several segment sequences exhibited alow discriminatory power in delineating its relationships. In this study, we characterized and comparatively analyzed the complete chloroplast (cp) genome of C. nanchuanica with those of six previously reported Cephalanthera species. Our findings revealed that the cp genome of C. nanchuanica had the typical quadripartite structure, with a size of 161,365bp and a GC content of 37.27%. A total of 113 unique genes were annotated, among which nearly half of protein-encoding genes (RSCU > 1) showed a preference in codon usage. No structural rearrangements were observed among the cp genomes of Cephalanthera species, except for C. humilis, which displayed structural alterations due to gene loss, relocation, and inverted repeat (IR) expansion/contraction. The cp genomes of Cephalanthera species were highly conserved, with only a small number of SSRs detected, most of which preferred A/T bases. Comparative analysis of cp genomes indicated that IR and coding regions were less divergent than single copy and non-coding regions and eight mutational hotspots were identified. Phylogenetic analysis suggested that the tribe Neottieae was a monophyletic group, divided into five clades. Palmorchis was the earliest-diverging lineage, followed by Cephalanthera. Diplandrorchis was deeply nested within Neottia, forming a clade. Aphyllorchis and Limodorum formed another clade, sister to Epipactis. Within the Cephalanthera clade, C. nanchuanica was sister to C. falcata with astrong support. This study demonstrated that the cp genome characters of C. nanchuanica are highly similar to those of other Cephalanthera species, except for the mycoheterotrophic species C. humilis. Although the cp genomes of Cephalanthera species (excluding C. humilis) exhibited conservation in genome structure and sequence, SSR repeats and mutational hotspots were identified, which could potentially serve as as molecular markers for distinguishing Cephalanthera species. The phylogenetic analysis based on the protein-coding genes provided high-resolution support for the infrageneric classification. Therefore, cp genome data will be instrumental in resolving the phylogeny of the genus Cephalanthera.

Whole-Genome Sequence and Characterization of Ralstonia solanacearum MLY102 Isolated from Infected Tobacco Stalks

Background/Objectives: Bacterial wilt disease is a soil-borne disease caused by Ralstonia solanacearum that causes huge losses to crop economies worldwide. Methods: In this work, strain MLY102 was isolated and further identified as R. solanacearum from a diseased tobacco stalk. The genomic properties of MLY102 were explored by performing biochemical characterization, genome sequencing, compositional analysis, functional annotation and comparative genomic analysis. Results: MLY102 had a pinkish-red color in the center of the colony surrounded by a milky-white liquid with fluidity on TTC medium. The biochemical results revealed that MLY102 can utilize carbon sources, including D-glucose (dGLU), cane sugar (SAC) and D-trehalose dihydrate (dTRE). Genome sequencing through the DNBSEQ and PacBio platforms revealed a genome size of 5.72 Mb with a G+C content of 67.59%. The genome consists of a circular chromosome and a circular giant plasmid with 5283 protein-coding genes. A comparison of the genomes revealed that MLY102 is closely related to GMI1000 and CMR15 but has 498 special genes and 13 homologous genes in the species-specific gene family, indicating a high degree of genomic uniqueness. Conclusions: The unique characteristics and genomic data of MLY102 can provide important reference values for the prevention and control of bacterial wilt disease.

Insights into brachyuran crab phylogeny: exploring the mitochondrial genome of Arcotheres sinensis (Brachyura, Pinnotheridae)

Abstract The phylogeny of species of Brachyura, particularly within the family Pinnotheridae, remains incompletely understood. To enhance the taxonomy and systematics of the Pinnotheridae, we conducted a comprehensive study aimed at elucidating the phylogenetic position of Arcotheres sinensis. Consequently, we sequenced and annotated the complete mitochondrial genome of A. sinensis, The results revealed that the circular mitogenome of A. sinensis spans 16 520 bp in length. Distinct from typical mitogenomes, A. sinensis contains 13 protein-coding genes (PCGs), 2 ribosomal RNA genes and 23 transfer RNA genes. The A + T content of the A. sinensis mitogenome is 71.63%, with both AT-skew and GC-skew being negative. The lengths of the 23 tRNA genes range from 62 to 72 bp. All tRNA genes exhibit typical cloverleaf structures, except for the trnS1 gene, which lacks the dihydrouridine (DHU) arm. Selection pressure analysis revealed that all PCGs are under evolutionary selection, with cox1 experiencing strongest purifying selection and atp8 undergoing weakest purifying selection. Compared to ancestral Brachyura, the gene order of A. sinensis has been rearranged from R-N--E to -E-N-R and the sequence I-Q-M has transitioned to Q-I-M. Phylogenetic analysis unequivocally positions A. sinensis within the taxonomic framework of the family Pinnotheridae, highlighting its intimate phylogenetic relationship with congeners within the same familial clade, notably Arcotheres purpureus and Pinnotheres excussus. These findings contribute to a better understanding of the status and evolutionary history of Pinnotheridae species.

A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives.

A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who's relatives had prostate-, and/or gastric cancer. The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model.Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case-control study. Candidate loci/genes on ten chromosomal regions were suggested with odds ratios between1.71-3.62 and p-values < 5 × 10-8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of DNA from 122 colorectal cancer patients with gastric- and/or prostate cancer in their families was performed to search for candidate variants in the haplotype regions. The identified candidate variants were tested in a nested case-control study of similar colorectal cancer cases and controls. There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested. This study demonstrated a proof of principle strategy to identify risk variants found by GWAS, and identified ten candidate loci that could be associated with colorectal, gastric- and prostate cancer.

The genome sequence of bronze sap hoverfly, Ferdinandea cuprea (Scopoli, 1763)

We present a genome assembly from an individual Ferdinandea cuprea (bronze sap hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence has a total length of 560.20 megabases. Most of the assembly (99.92%) is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.0 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,662 protein-coding genes.

Abstract A013: Molecular mechanisms of intron retention in Long Non-Coding RNAs

Abstract Intron retention (IR) is a form of alternative splicing in which an intron that should be spliced out from a precursor transcript, is retained in the mature RNA after the splicing is completed. Although there is emerging evidence of widespread IR in protein-coding genes and long noncoding RNAs (lncRNAs), the underlying molecular mechanisms remain largely unclear. Here, we report the discovery of novel transcripts from the p53-induced lncRNA PURPL, in which intron 2 is retained. To determine the molecular mechanism(s) of IR in PURPL, we conducted a CRISPR-based screen in 3 different cell lines. For this purpose, we utilized a genome-wide guide RNA library expressing a reporter minigene containing the sequence of PURPL intron 2 and its flanking exons. Considering the Percent Intron Retention as readout, we unexpectedly identified proteins of the basal splicing machinery as potential promoting factors of PURPL IR, including the U2-Auxiliary Factor 2 (U2AF2) splicing factor which was one of the top hits of the screen. We next analyzed ENCODE eCLIP-seq datasets to identify RNA binding proteins that could regulate intron 2 and decided to focus on U2AF2 which showed the highest number of binding sites and strongest eCLIP signals within PURPL intron 2 sequence. We validated the effect of U2AF2 by knocking it down, confirming that U2AF2 is a positive regulator of PURPL intron 2 retention as opposed to its canonical function. We also identified the RNA Binding Protein SON as a splicing regulator that acts as an antagonist of U2AF2 in regulating PURPL intron 2 retention. To determine the global impact of U2AF2 knockdown, we performed Iso-Seq and RNA-seq upon U2AF2 depletion. We found that although U2AF2 predominantly acts to promote the splicing of introns in most cellular transcripts, it promotes intron retention in a subset of transcripts. One of these targets is MALAT1, a lncRNA known to play role in splicing by interacting with splicing factors in nuclear speckles. Interestingly, U2AF2 depletion results in MALAT1 exclusion from nuclear speckles. We are currently in the process of characterizing the effect of U2AF2 in the function of the two lncRNAs. These data provide mechanistic insights on PURPL and MALAT1 splicing and function and reveal a previously unrecognized non-canonical function of U2AF2 in promoting intron retention. Citation Format: Ioannis Grammatikakis, Amit Behera, Corrine Corrina R Hartford, Erica C Pehrsson, XiaoLing Li, Yongmei Zhao, Biraj Shrethsa, Tayvia Brownmiller, Natasha J Caplen, Kannanganattu V Prasanth, Thomas Gonatopoulos-Pournatzis, Ashish Lal. Molecular mechanisms of intron retention in Long Non-Coding RNAs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A013.

Draft genome sequence of Bacillus thuringiensis serovar. toumanoffi NRRL B-4059: identification of a novel Cry protein candidate.

Here, we report the high-quality draft genome of Bacillus thuringiensis serovar. toumanoffi NRRL B-4059, with a complete circular chromosome and nine circular plasmids. The assembly is 7,031,170 bp and encodes 6,974 protein-coding genes, 42 rRNA genes, 107 tRNA genes, and has 34.7% GC content. Nine genes encoding Cry proteins were identified, including one previously unidentified Cry protein candidate.

Comparison of GWAS results between de novo tinnitus and cancer treatment-related tinnitus suggests distinctive roles for genetic risk factors.

Tinnitus is a common sensorineural complication that can occur de novo or after cancer treatments involving cisplatin or radiotherapy. Considering the heterogeneous etiology and pathophysiology of tinnitus, the extent to which shared genetic risk factors contribute to de novo tinnitus and cancer treatment-induced tinnitus is not clear. Here we report a GWAS for de novo tinnitus using the UK Biobank cohort with nine loci showing significantly associated variants (p < 5 × 10-8). To our knowledge, significant associations in four of these loci are novel, represented by rs7336872, rs115125870, rs1532898 and rs2537, with UBAC2, NUDT9, TGM4 and MPP2 as their nearest protein coding genes, respectively. Through quantitative comparison of results from GWAS of de novo tinnitus with GWAS of radiation-induced tinnitus, two intronic variants (rs7023227 and rs3780395) from a locus within immunoregulatory gene PD-L1 (CD274) reached the replication threshold using comparison thresholds of 10-5 and 10-4, with no other shared genetic risk factors identified. We did not observe shared genetic risk factors between de novo and cisplatin-induced tinnitus. Our results suggest that genetic risk factors are mainly distinct based on etiology of tinnitus and future efforts to study, prevent or treat tinnitus are expected to benefit from strategies that allow for distinction of cases based on the primary environmental risk factor.

Chromosome-level genome assembly of Indo-Pacific king mackerel (Scomberomorus guttatus).

The Indo-Pacific king mackerel, scientifically known as Scomberomorus guttatus, is a valued marine species that holds significant commercial importance in the Indo-Pacific region. However, the lack of genomic resources has hindered a comprehensive understanding of this species. In this study, we constructed a genome of Indo-Pacific king mackerel at the chromosome level using a combination of PacBio HiFi reads and a chromosome contact map (Hi-C). The resulting genome had high contig and scaffold N50 values of 8.84 Mb and 32.9 Mb, respectively. In the genome assembly, which is 797.66 Mb in size and consists of 24 chromosomes, we also identified 35.89% repetitive elements and predicted 25,886 protein-coding genes. Our study not only benefits to reveal the possible mechanism of adaptive evolution in this fish, but also offers insight for the future sustainable management of these valuable biological resources.

Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.

Infertility is a multifactorial reproductive system disorder,and most infertility cases occur inmen. Semen testing is now thought to be the most important diagnostic test for infertile men; nonetheless, because of its limitations, the cause of infertility remains unknown for 40% of infertile men. Semen assessment's shortcomings indicate the need for improved and innovative diagnostic techniques and biomarkers worldwide. Non-coding RNAs with a length of roughly 18-22 nucleotides are called microRNAs (miRNAs). Most of our protein-coding genes are post-transcriptionally regulated by them. These molecules are unusual in bodily fluids, and aberrant variations in their expression can point to specific conditions like infertility. As a result, fresh potential biomarkers for the diagnosis and prognosis of various forms of male infertility may be represented by miRNAs. This reviewexamined the most recent research revealing the association between different miRNAs' functions in male infertility and their expression patterns. Also, it aims to figure out the most recent strategies that could be applied for using such miRNAs as possible therapeutic targets for infertility treatment.

A Whole-Genome Survey and the Mitochondrial Genome of Acanthocepola indica Provide Insights into Its Phylogenetic Relationships in Priacanthiformes

Acanthocepola indica, a deep-sea snake fish, is primarily found in the Indo-west Pacific region, including India, Korea, Japan, and the South China Sea. The taxonomic classification of A. indica based on morphological characteristics remains inaccurate and unclear. In this study, we utilized next-generation sequencing to generate comprehensive genomic data for A. indica. The estimated genome size of A. indica was 422.95 Mb, with a heterozygosity ratio of 1.02% and a sequence repeat ratio of 22.43%. Our analysis suggested that A. indica is diploid, and the draft genome assembly consists of 1,059,784 contigs with a contig N50 of 1942 bp. We identified a total of 444,728 simple sequence repeats in the genome of A. indica. Furthermore, we successfully assembled the complete mitochondrial genome (16,439 bp) of A. indica, which included 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes. Phylogenetic analysis based on mitochondrial genomes revealed that A. indica is closely related to Acanthocepola krusensternii and Cepola schlegelii, providing evidence that the family Cepolidae belongs to the order Priacanthiformes. Population size dynamics analysis indicated that A. indica experienced a bottleneck effect during the Pleistocene Glacial Epoch, likely due to the changes in glacial cycles and sea level fluctuations since ~800 Kya.

Chromosome-level genome assembly of the cave leech Sinospelaeobdella cavatuses (Hirudinea: Haemadipsidae).

Leeches are famous for their high medical value and wide environmental adaptability. Among them, cave leeches are a very fascinating and rare group, which is an important component in the study of adaptive evolution of leeches. However, no study has yet reported a reference genome for this group. In this study, we assembled a high-quality chromosome-level genome of the cave terrestrial leech Sinospelaeobdella cavatuses, through Illumina and PacBio sequencing, alongside chromosome conformation capture techniques. The resulting genome spans 153.67 Mb across 9 pseudochromosomes(range: 11.33 to 23.53 Mb), with a mounting rate of up to 95.37% and features an N50 length of 17.15 Mb. This genome is composed of 35.16% repetitive elements and contains 21180 predicted protein-coding genes. Decoding the S. cavatuses genome not only promotes future studies on study of its phylogeny, evolution, and behavior, but also provides valuable resources for in-depth investigation on adaptive evolution of leech.

Abstract 4117767: Interplay Between ST2 Gene Downregulation and Inflammatory Processes in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease and the pathogenesis of HCM involves genetic mutations, hemodynamic stress, and metabolic factors, with myocardial fibrosis playing a crucial role in severe clinical events. IL-33/ST2 signaling pathway known for its roles in immune response and tissue repair, participates in cardiac protection and anti-cardiac fibrosis in heart failure. The role of ST2 in HCM remains unclear, and IL-33/ST2 pathway and broader inflammatory responses may be critical in HCM. Hypothesis: ST2 gene downregulation and dysregulation of inflammatory pathways represent a novel mechanism in HCM. Methods: We re-analyzed the raw whole transcriptome sequencing data using a comprehensive bioinformatics pipeline from 9 GEO datasets. After removing low-quality samples, myocardial tissue samples from 109 HCM patients and 210 non-HCM controls were included. HTSeq-count was used to obtain the read count of each gene. Differential expression analyses were conducted using DESeq2. Spearman correlation analysis was performed for ST2 with all other protein-coding genes. Gene set enrichment analysis (GSEA) was performed to explore the biological significance of ST2 related genes. CIBERSORTx was used to estimate the immune cell composition of heart tissues. Additionally, network analyses and statistical correlations were conducted. Results: Our analysis identified significant downregulation of the ST2 gene in HCM patients compared to controls (log2FC = -5.0, p = 2.7E-147). In total, 5,180 upregulated and 741 downregulated genes were detected. Additionally, 208 genes were significantly correlated with the expression of ST2. GSEA based on the correlation coefficients revealed a significant increase in immune response, inflammation, and IFN-γ pathway activity, along with a decrease in the expression of genes related to sarcomeric function, cardiac morphogenesis, and metabolism in HCM. Notably, the significant inverse correlation between ST2 expression and regulatory T cells (r = -0.34) and a positive correlation with neutrophils (r = 0.39) suggest that ST2 may modulate immune cell populations in HCM. Pathway analysis indicated ST2's central role in networks involving inflammatory and fibrotic responses. Conclusion: The interplay between ST2 and inflammatory pathways may drive myocardial remodeling and fibrosis in HCM. This study paves a new way for investigating pathogenic mechanisms and therapeutic strategies for HCM.

The genome sequence of a lauxaniid fly, Calliopum simillimum (Collin, 1933)

We present a genome assembly from an individual male Calliopum simillimum (Arthropoda; Insecta; Diptera; Lauxaniidae). The genome sequence has a total length of 690.50 megabases. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.18 kilobases in length. Gene annotation of this assembly on Ensembl identified 32,839 protein-coding genes.