Efficient test for deviation from Hardy-Weinberg equilibrium with known or ambiguous typing in highly polymorphic loci.

The Hardy-Weinberg equilibrium (HWE) assumption is essential to many population genetics models. Multiple tests were developed to test its applicability in observed genotypes. Current methods are divided into exact tests applicable to small populations and a small number of alleles, and approximate goodness-of-fit tests.

Microbiome signature of posttraumatic stress disorder and resilience in youth.

Objective: Identifying biomarkers that can distinguish trauma-exposed youth at risk for developing posttraumatic pathology from resilient individuals is essential for targeted interventions. As trauma can alter the microbiome with lasting effects on the host, our longitudinal, multimeasure, cross-species study aimed to identify the microbial signature of posttraumatic stress disorder (PTSD).

Method: We followed children exposed to war-related trauma and matched controls from early childhood ( = 2.

Graph-Based Imputation Methods and Their Applications to Single Donors and Families.

The outcome of Hematopoietic Stem Cell (HSCT) and organ transplant is strongly affected by the matching of the HLA alleles of the donor and the recipient. However, donors and sometimes recipients are often typed at low resolution, with some alleles either missing or ambiguous. Thus, imputation methods are required to detect the most probably high-resolution HLA haplotypes consistent with a typing.

Prediction of KIR3DL1/Human Leukocyte Antigen binding.

KIR3DL1 is a polymorphic inhibitory Natural Killer (NK) cell receptor that recognizes Human Leukocyte Antigen (HLA) class I allotypes that contain the Bw4 motif. Structural analyses have shown that in addition to residues 77-83 that span the Bw4 motif, polymorphism at other sites throughout the HLA molecule can influence the interaction with KIR3DL1. Given the extensive polymorphism of both KIR3DL1 and HLA class I, we built a machine learning prediction model to describe the influence of allotypic variation on the binding of KIR3DL1 to HLA class I.

mi-Mic: a novel multi-layer statistical test for microbiota-disease associations.

mi-Mic, a novel approach for microbiome differential abundance analysis, tackles the key challenges of such statistical tests: a large number of tests, sparsity, varying abundance scales, and taxonomic relationships. mi-Mic first converts microbial counts to a cladogram of means. It then applies a priori tests on the upper levels of the cladogram to detect overall relationships.

Validation of the first-trimester machine learning model for predicting pre-eclampsia in an Asian population.

Objectives: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population.

Methods: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1).

Qualitative, rather than quantitative, differences between HLA-DQ alleles affect HLA-DQ immunogenicity in organ transplantation.

Prolonging the lifespan of transplanted organs is critical to combat the shortage of this life-saving resource. Chronic rejection, with irreversible demise of the allograft, is often caused by the development of donor-specific HLA antibodies. Currently, enumerating molecular (amino acid) mismatches between recipient and donor is promoted to identify patients at higher risk of developing HLA antibodies, for use in organ allocation, and immunosuppression-minimization strategies.

The Cross-talk Between Intestinal Microbiota and MDSCs Fuels Colitis-associated Cancer Development.

Unlabelled: Intestinal chronic inflammation is associated with microbial dysbiosis and accumulation of various immune cells including myeloid-derived suppressor cells (MDSC), which profoundly impact the immune microenvironment, perturb homeostasis and increase the risk to develop colitis-associated colorectal cancer (CAC). However, the specific MDSCs-dysbiotic microbiota interactions and their collective impact on CAC development remain poorly understood. In this study, using a murine model of CAC, we demonstrate that CAC-bearing mice exhibit significantly elevated levels of highly immunosuppressive MDSCs, accompanied by microbiota alterations.

Single-residue linear and conformational B cell epitopes prediction using random and ESM-2 based projections.

B cell epitope prediction methods are separated into linear sequence-based predictors and conformational epitope predictions that typically use the measured or predicted protein structure. Most linear predictions rely on the translation of the sequence to biologically based representations and the applications of machine learning on these representations. We here present CALIBER 'Conformational And LInear B cell Epitopes pRediction', and show that a bidirectional long short-term memory with random projection produces a more accurate prediction (test set AUC=0.

Gut microbiome-metabolome interactions predict host condition.

Background: The effect of microbes on their human host is often mediated through changes in metabolite concentrations. As such, multiple tools have been proposed to predict metabolite concentrations from microbial taxa frequencies. Such tools typically fail to capture the dependence of the microbiome-metabolite relation on the environment.

Bw4 ligand and direct T-cell receptor binding induced selection on HLA A and B alleles.

Introduction: The HLA region is the hallmark of balancing selection, argued to be driven by the pressure to present a wide variety of viral epitopes. As such selection on the peptide-binding positions has been proposed to drive HLA population genetics. MHC molecules also directly binds to the T-Cell Receptor and killer cell immunoglobulin-like receptors (KIR).

Combined imputation of HLA genotype and self-identified race leads to better donor-recipient matching.

Allogeneic Hematopoietic Cell Transplantation (HCT) is a curative therapy for hematologic disorders and often requires human leukocyte antigen (HLA)-matched donors. Donor registries have recruited donors utilizing evolving technologies of HLA genotyping methods. This necessitates in-silico ambiguity resolution and statistical imputation based on haplotype frequencies estimated from donor data stratified by self-identified race and ethnicity (SIRE).

Shared bias in H chain V-J pairing in naive and memory B cells.

Introduction: H chain rearrangement in B cells is a two-step process where first binds , and only then is joined to the complex. As such, there is no direct rearrangement between and .

Results: Nevertheless, we here show that the JH combinations frequency in humans deviates from the one expected based on each gene usage frequency.

Is there a difference in labor patterns after induction with prostaglandins and double-balloon catheters?

Background: Labor progression curves are believed to differ between spontaneous and induced labors. However, data describing labor progression patterns with different modes of induction are insufficient.

Objective: This study aimed to compare the progress patterns between labors induced with slow-release prostaglandin E vaginal analogue and those induced with a double-balloon catheter.

Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.

Background: Some microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT).

Ordering taxa in image convolution networks improves microbiome-based machine learning accuracy.

The human gut microbiome is associated with a large number of disease etiologies. As such, it is a natural candidate for machine-learning-based biomarker development for multiple diseases and conditions. The microbiome is often analyzed using 16S rRNA gene sequencing or shotgun metagenomics.

Trans-population graph-based coverage optimization of allogeneic cellular therapy.

Background: Pre-clinical development and in-human trials of 'off-the-shelf' immune effector cell therapy (IECT) are burgeoning. IECT offers many potential advantages over autologous products. The relevant HLA matching criteria vary from product to product and depend on the strategies employed to reduce the risk of GvHD or to improve allo-IEC persistence, as warranted by different clinical indications, disease kinetics, on-target/off-tumor effects, and therapeutic cell type (T cell subtype, NK, etc.

GRAMM: A new method for analysis of HLA in families.

Recently, haplo-identical transplantation with multiple HLA mismatches has become a viable option for stem cell transplants. Haplotype sharing detection requires the imputation of donor and recipient. We show that even in high-resolution typing when all alleles are known, there is a 15% error rate in haplotype phasing, and even more in low-resolution typings.

New Insights on DR and DQ Human Leukocyte Antigens in Anti-LGI1 Encephalitis.

Background And Objectives: To explore the clinical characteristics and HLA associations of patients with anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel. Anti-LGI1E is the most commonly diagnosed antibody-associated encephalitic syndrome in adults. Recent studies of various populations reveal significant associations with specific HLA genes.

Naive and memory T cells TCR-HLA-binding prediction.

T cells recognize antigens through the interaction of their T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC) molecule. Following thymic-positive selection, TCRs in peripheral naive T cells are expected to bind MHC alleles of the host. Peripheral clonal selection is expected to further increase the frequency of antigen-specific TCRs that bind to the host MHC alleles.

Counting is almost all you need.

The immune memory repertoire encodes the history of present and past infections and immunological attributes of the individual. As such, multiple methods were proposed to use T-cell receptor (TCR) repertoires to detect disease history. We here show that the counting method outperforms two leading algorithms.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

Objective: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities.

Design: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis.