Mendelian diseases tend to manifest clinically in certain tissues, yet their affected cell types typically remain elusive. Single-cell expression studies showed that overexpression of disease-associated genes may point to the affected cell types. Here, we developed a method that infers disease-affected cell types from the preferential expression of disease-associated genes in cell types (PrEDiCT). We applied PrEDiCT to single-cell expression data of six human tissues, to infer the cell types affected in Mendelian diseases. Overall, we inferred the likely affected cell types for 328 diseases. We corroborated our findings by literature text-mining, expert validation, and recapitulation in mouse corresponding tissues. Based on these findings, we explored characteristics of disease-affected cell types, showed that diseases manifesting in multiple tissues tend to affect similar cell types, and highlighted cases where gene functions could be used to refine inference. Together, these findings expand the molecular understanding of disease mechanisms and cellular vulnerability.

Background: Placental abruption (PA) is an unpredictable obstetric complication associated with substantial maternal and fetal/neonatal morbidity and mortality in the index and subsequent pregnancies. The previous PA severity classification categorizes more than two-thirds of cases as severe, which limits its clinical utility despite its association with adverse maternal outcomes. Objective: We aimed to develop a novel, clinically applicable PA severity classification and to determine its ability to predict its recurrence in subsequent pregnancies. Study design: This retrospective, population-based cohort study included medical records of all women who delivered at our medical center from 2001 to 2021. Pregnancies complicated by chromosomal abnormalities or major congenital anomalies were excluded. The novel PA severity classification included maternal (transfusion of ≥4 units of red blood cells, admission to an intensive care unit, DIC, hysterectomy, or maternal death) and neonatal (birth asphyxia, hypoxic–ischemic encephalopathy, umbilical cord blood acidosis defined as pH < 7.0, neonatal intensive care unit admission at ≥35 weeks gestation, or perinatal death) complications. Maternal characteristics, clinical features, and perinatal outcomes were compared between the novel and the existing PA severity classifications. A multivariate regression model was used to determine the association between PA severity and the risk of its recurrent in subsequent pregnancies. Results: Our cohort included 298,281 deliveries; of them, 1567 (0.5%) had PA. The rate of severe PA was lower in the novel vs. the existing classification (p < 0.001). Within the novel classification, severe PA was associated with higher rates of mild and severe preeclampsia and lower mean fibrinogen concentrations and platelet counts compared with mild abruption (all p < 0.001). Severe PA was independently associated with an increased risk of recurrence in subsequent pregnancies (OR 1.82, 95% CI 1.05–3.14). Conclusions: We propose a novel, clinically relevant PA severity classification that accurately identifies severe disease providing prognostic information regarding the risk of PA recurrence in future pregnancies.

Background: Placental abruption (PA) is an unpredictable obstetric complication associated with substantial maternal and fetal/neonatal morbidity and mortality, in the index and subsequent pregnancies. The currentPA severity classification categorises more than two-thirds of cases as severe, which limits its clinical utility despite its association with adverse maternal outcomes. We aimed to develop a novel, clinically applicable PA severity classification and to detrmine its ability to predict its recurrence in subsequent pregnancies.Methodes: This retrospective, population-based cohort study included medical records of all women who delivered at our medical centre from 2001-2021. Pregnancies complicated by chromosomal abnormalities or major congenital anomalies were excluded. The novel PA severity classification included maternal (transfusion of ≥4 units of red blood cells, admission to an intensive care unit, DIC, hysterectomy, or maternal death) and neonatal (birth asphyxia, hypoxic–ischaemic encephalopathy, umbilical cord blood acidosis defined as pH <7·0, neonatal intensive care unit admission at ≥35 weeks gestation, or perinatal death) complications. Maternal characteristics, clinical features, and perinatal outcomes were compared between the novel and the existing PA severity classifications. Multivariate regression models were used to detrmine the association between PA severity and the risk of its recurrent in subsequent pregnancies.Findings: Our cohort included 298 281 deliveries, of them 1 567 (0·5%) had PA. The rate of severe PA was lower in the novel vs. The existing classification (p<0·001). Within the novel classification, severe PA was associated with higher rates of mild and severe preeclampsia, lower mean fibrinogen concentrations, and platelet count compared with mild abruption (all p<0·001). Severe PA was independently associated with an increased risk of recurrence in subsequent pregnancies (OR 1·82, 95% CI 1·05–3·14).Interpretation: We propose a novel, clinically relevant PA severity classification that accurately identifies severe disease providing prognostic information regarding the risk of PA recurrence in future pregnancies.