Microbiome studies have revealed gut microbiota's potential impact on complex diseases. However, many studies often focus on one disease per cohort. We developed a meta-analysis workflow for gut microbiome profiles and analyzed shotgun metagenomic data covering 11 diseases. Using interpretable machine learning and differential abundance analysis, our findings reinforce the generalization of binary classifiers for Crohn's disease (CD) and colorectal cancer (CRC) to hold-out cohorts and highlight the key microbes driving these classifications. We identified high microbial similarity in disease pairs like CD vs ulcerative colitis (UC), CD vs CRC, Parkinson's disease vs type 2 diabetes (T2D), and schizophrenia vs T2D. We also found strong inverse correlations in Alzheimer's disease vs CD and UC. These findings detected by our pipeline provide valuable insights into these diseases.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.
Autism Spectrum Disorder , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Brain-Gut Axis , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/metabolism , Cross-Sectional Studies , Bayes Theorem , Reproducibility of Results , Cytokines
The typical plastid genome (plastome) of photosynthetic angiosperms comprises a pair of Inverted Repeat regions (IRs), which separate a Large Single Copy region (LSC) from a Small Single Copy region (SSC). The independent losses of IRs have been documented in only a few distinct plant lineages. The majority of these taxa show uncommonly high levels of plastome structural variations, while a few have otherwise conserved plastomes. For a better understanding of the function of IRs in stabilizing plastome structure, more taxa that have lost IRs need to be investigated. We analyzed the plastomes of eight species from two genera of the putranjivoid clade of Malpighiales using Illumina paired-end sequencing, the de novo assembly strategy GetOrganelle, as well as a combination of two annotation methods. We found that all eight plastomes of the putranjivoid clade have lost their IRB, representing the fifth case of IR loss within autotrophic angiosperms. Coinciding with the loss of the IR, plastomes of the putranjivoid clade have experienced significant structural variations including gene and intron losses, multiple large inversions, as well as the translocation and duplication of plastome segments. However, Balanopaceae, one of the close relatives of the putranjivoid clade, exhibit a relatively conserved plastome organization with canonical IRs. Our results corroborate earlier reports that the IR loss and additional structural reorganizations are closely linked, hinting at a shared mechanism that underpins structural disturbances.
The clusioid clade of Malpighiales is comprised of five families: Bonnetiaceae, Calophyllaceae, Clusiaceae, Hypericaceae and Podostemaceae. Recent studies have found the plastome structure of Garcinia mangostana L. from Clusiaceae was conserved, while plastomes of five riverweed species from Podostemaceae showed significant structural variations. The diversification pattern of plastome structure of the clusioid clade worth a thorough investigation. Here we determined five complete plastomes representing four families of the clusioid clade. Our results found that the plastomes of the early diverged three families (Clusiaceae, Bonnetiaceae and Calophyllaceae) in the clusioid clade are relatively conserved, while the plastomes of the other two families show significant variations. The Inverted Repeat (IR) regions of Tristicha trifaria and Marathrum foeniculaceum (Podostemaceae) are greatly reduced following the loss of the ycf1 and ycf2 genes. An inversion over 50 kb spanning from trnK-UUU to rbcL in the LSC region is shared by Cratoxylum cochinchinense (Hypericaceae), T. trifaria and Ma. foeniculaceum (Podostemaceae). The large inversed colinear block in Hypericaceae and Podostemaceae contains all the genes in the 50-kb inversed colinear block in a clade of Papilionoideae, with two extra genes (trnK-UUU and matK) at one end. Another endpoint of both inversions in the two clusioids families and Papilionoideae is located between rbcL and accD. This study greatly helped to clarify the plastome evolution in the clusioid clade.
Clusiaceae/genetics , Evolution, Molecular , Genome, Plastid , Malpighiales/genetics , Plastids/genetics , DNA, Plant/genetics , Phylogeny , Sequence Analysis, DNA
Klainedoxa gabonensis Pierre ex Engl. is an important tropical tree species. In this study, its complete plastome sequence was determined. This is the first reported complete plastome sequence in the family Irvingiaceae. The plastome is totally 160,118 bp in length, containing a pair of 26,963-bp-long inverted repeat regions (IRs), a large single copy region of 88,157 bp, and a small single copy region of 18,035 bp. A total of 112 unique genes were identified in K. gabonensis plastome, of which 78 are protein-coding genes, 30 are tRNA genes, and four are rRNA genes. Phylogenetic analysis confirmed the close relationship between K. gabonensis and Irvingia malayana.
Ctenolophon englerianus Mildbr. is endemic to West Africa. The wood of this species is very strong, and is widely used as building material in local regions. In this study, we determined its complete plastome sequence. This is the first reported complete plastome sequence in the family Ctenolophonaceae. The plastome of C. englerianus was found to possess a total length of 161,553 bp containing two inverted repeats (IRs) of 27,469 bp, a large single copy (LSC) region of 89,386 bp, and a small single copy (SSC) region of 17,229 bp. The plastome contains 110 unique genes, consisting of 76 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The rpl32, rps16 and infA genes were lost. To validate the phylogenetic relationships of C. englerianus in Malpighiales, we have selected seven representative families from three major clades of Malpighiales to construct phylogenetic tree. According to the phylogenetic topologies, C. englerianus has a close relationship with Erythroxylum novogranatence.
