bioRxiv Science⌕ Search

Biology subjects

Reynoso, S.

Publications and source records attributed to Reynoso, S..

2 recordsLinked to original sources

STEAM: Spatial Transcriptomics Evaluation Algorithm and Metric for clustering performance

MotivationSpatial transcriptomic technologies allow researchers to explore the diversity and specificity of gene expression within their original tissue structure. Accurately identifying regions that are spatially coherent in both gene expression and physical tissue structures is an emerging topic, but challenging due to the lack of ground truth labels which renders complicating validation of clustering consistency and reproducibility. This highlights a need for a computational evaluation framework to rigorously and unbiasedly assess clustering performance. ResultsTo address this gap, we propose STEAM (Spatial Transcriptomics Evaluation Algorithm and Metric), a user-friendly computational pipeline designed to evaluate the consistency and reliability of clustering results by leveraging machine learning classification and prediction methods, with the goal of maintaining the spatial proximity and gene expression patterns within clusters. We benchmarked STEAM on various public datasets, spanning multi-cell to single-cell resolution, as well as spatial transcriptomics and proteomics. The results highlighted its robustness and generalizability through comprehensive statistical evaluation metrics, such as Kappa score, F1 score, accuracy, and adjusted rand index. Notably, STEAM supports multi-sample training, enabling cross-replicate clustering consistency assessment. Moreover, STEAM provides practical guidance by comparing clustering results across multiple approaches; here, we evaluated four different methods, including spatial-aware and spatial-ignorant approaches. In summary, we believe that STEAM provides researchers a promising tool for evaluating clustering robustness and benchmarking clustering performance for spatial omics data, offering valuable insights to drive reproducible discoveries in spatial biology. Availability and implementationSource code and the R software tool STEAM are available from https://github.com/fanzhanglab/STEAM.

bioinformatics↗

GIV/Girdin, a Non-receptor Modulator for Gαi/s, Regulates Spatiotemporal Signaling during Sperm Capacitation and is Required for Male Fertility

For a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract, and later undergo acrosomal reaction (AR) upon encountering an egg surrounded by its vestment. How premature AR is avoided despite rapid surges in signaling cascades during capacitation remains unknown. Using a combination of KO mice and cell-penetrating peptides, we show that GIV (CCDC88A), a guanine nucleotide-exchange modulator (GEM) for trimeric GTPases, is highly expressed in spermatocytes and is required for male fertility. GIV is rapidly phosphoregulated on key tyrosine and serine residues in human and murine spermatozoa. These phosphomodifications enable GIV-GEM to orchestrate two distinct compartmentalized signaling programs in the sperm tail and head; in the tail, GIV enhances PI3K[->] Akt signals, sperm motility and survival, whereas in the head it inhibits cAMP surge and premature AR. Furthermore, GIV transcripts are downregulated in the testis and semen of infertile men. These findings exemplify the spatiotemporally segregated signaling programs that support sperm capacitation and shed light on a hitherto unforeseen cause of infertility in men. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/442927v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@f4901forg.highwire.dtl.DTLVardef@2211dforg.highwire.dtl.DTLVardef@c37ff5org.highwire.dtl.DTLVardef@105eed7_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIGIV is highly expressed in spermatozoa, and is required for male fertility C_LIO_LIGIV is rapidly phosphoregulated during sperm capacitation C_LIO_LIIt enhances tyrosine-based signals in sperm tail, enhances motility C_LIO_LIIt suppresses cAMP in the sperm head, inhibits premature acrosome exocytosis C_LI

cell biology↗