Learn more about this joint special issue from Cell Genomics, Cell Reports, and iScience.

September 17-19, 2025 | San Diego, CA, USA.

Read papers by the winners and other relevant research published in Cell Press journals.

September 26, 2024; 12:00 pm ET | Register for live & on demand access.

In this issue of Cell Genomics, Jin et al. present a series of articles based on sequencing data from non-invasive prenatal testing (NIPT) in pregnant women, focusing on multiple phenotypes and diseases. The cover image represents these articles. On the left is the silhouette of a pregnant woman; surrounding the fetus in her womb are the radial rings of Manhattan plots, representing the main content of this series as genome-wide association studies based on the pregnant woman's genome. The right side of the image contains a blood tube with a DNA molecule leaping out of it, representing that the samples used in these studies are from the cell-free DNA in the blood drawn from the pregnant woman's NIPT examination. Artist credit: Huanhuan Zhu and Linxuan Li, authors from this series of articles, jointly completed the conceptual design of this cover, with Linxuan Li completing the graphic illustration.

The molecular mechanisms underlying the paradoxical effects of aneuploidy are still not completely understood. In this issue, Rojas et al. systematically analyzed the associated costs of aneuploidy and the molecular drivers involved, which revealed that aneuploidy stress is primarily driven by the cumulative effects of genes per chromosome. Notably, gene length was predicted as the most significant indicator of aneuploidy toxicity by machine learning.

Human milk has long been recognized for its critical role in infant and maternal health. In this issue of Cell Genomics, Johnson et al. apply a human genetics and genomics approach to shed light on the complex relationship between maternal genetics, milk variation, and the infant gut microbiome.

Guo et al. studied the association between 5,957,600 variants and 317 disease phenotypes in 25,639 Chinese pregnant women and 14,151 newborns using NIPT and EHR data. This study informed potential associations between maternal and neonatal diseases, offering insights into risk loci predisposing comorbidities of mothers and children.

Liu et al. introduce and evaluate the NIPT-human-genetics workflow, which integrates probabilistic models for analyzing large-scale, low-depth NIPT sequencing data. This workflow includes customized algorithms and software for detecting genetic variation detection, imputing genotypes, inferring population structure and family relatedness, and conducting genome-wide association analysis of maternal genomes.

Zhu et al. analyzed 14,744 Chinese pregnant women, identifying 25 genetic associations with glycemic traits via GWAS. They discovered a novel link between fasting glucose and the ESR1 gene and validated this by an independent study. Further analyses provided a genetic insight into the relationship between pregnancy glycemic traits and hypertension.

Xiao et al. performed a genetic analysis of 104 pregnancy phenotypes in 20,900 Chinese women. The GWAS identified 410 trait-locus associations, with 71.71% reported previously. Of 116 novel hits, 83 were successfully replicated. Among them, 31 were defined as potentially pregnancy-specific associations, revealing enrichments in estrogen-related pathways and female reproductive tissues.

He et al. imputed 5.4 million SNPs from 27,785 low-pass whole-genome sequencing data obtained through non-invasive prenatal testing in pregnant women. They utilized the SNPs from maternal genomes to identify genetic factors contributing to 75 metabolic components in newborns. The results revealed 19 associations previously established in adults, along with 11 novel associations, and an average heritability of 76.2% for neonatal metabolites.

A large-scale genome-wide association study (GWAS) elucidates the genetic basis of 84 maternal plasma metabolites during pregnancy, identifying 53 metabolite-gene associations, of which 23 are novel. Pregnancy-specific genetic effects were found in 16.7%–100% of these associations. Pleiotropy was observed in 50.94% of the associations among metabolites and between six metabolites and eight pregnancy phenotypes. Potential causal relationships were identified between 7 maternal metabolites and 15 human traits or diseases.

Ni et al. introduce PertKGE, a method that deconvolutes compound-protein interactions using a novel biological knowledge graph. PertKGE excels in drug discovery tasks, including target inference and virtual screening. The study reveals the unique anti-tumor immunotherapy effect of tankyrase inhibitor K-756 and identified five new hits for a promising cancer target, ALDH1B1.

Why extra chromosomes are harmful to cells has been difficult to understand. Rojas et al. use molecular analysis, statistical modeling, and model validation in eukaryotic budding yeast. A multi-factorial model explains a large portion of the variance in chromosome costs. This model includes the cumulative cost of single-gene duplications, deleterious effects of snoRNAs, and beneficial effect of tRNAs on each chromosome. This work presents a framework for understanding the cost of aneuploidy, with implications for evolution, developmental disorders, and cancer.

Sun et al. assembled a loach haplotype-resolved genome and identified a fish air-breathing gene, Mex3a, which could regulate angiogenesis through its interaction with Tbx20. Their findings hold significant implications for understanding the evolution of fish air breathing and provide a valuable resource for cultivating hypoxia-tolerant fish varieties.

Cao et al. illustrate the anti-tumor immunotherapy efficacy of CXCR4 blockades and its role in modulating the functional and exhausted CD8⁺ T cell phenotypes by regulating the JAK2-STAT3 pathway. This work supports the combined use of CXCR4 inhibitors and immune checkpoint blockades in clinical trials for cancer treatment.

Yu et al. introduce FUSE, a framework that reduces statistical noise in functional screening datasets by analyzing experimental results collectively. By leveraging data from 115 functional assays, FUSE improves estimates of functional effects and variant classification accuracy, providing valuable insights for clinical and research applications in genomics.

Human milk has positive health impacts for lactating parents and infants, and milk composition varies across individuals. Johnson et al. perform an eQTL study of human milk cells and link the milk transcriptome to maternal traits, milk composition, and the infant gut microbiome.

Ueda et al. discover that changes in transcript isoforms can alter the function of immune response genes in human B cells. These changes help explain how the body fights infections and regulates the immune system, emphasizing the role of gene splicing in health and disease.

Serebrenik et al. develop a method for pooled induction of ectopic protein-protein interactions by combining gene tagging using a ligand-binding domain with generic heterobifunctional small molecules. They then screen for effector proteins with degradative function and identify members of the multi-subunit C-terminal-to-LisH (CTLH) complex, specifically WDR26, as potent degraders.