Genomes of multicellular algal sisters to land plants illuminate signaling network evolution.

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

Defining severity of personality disorder using electronic health records: short report.

Severity of personality disorder is an important determinant of future health. However, this key prognostic variable is not captured in routine clinical practice. Using a large clinical data-set, we explored the predictive validity of items from the Health of Nation Outcome Scales (HoNOS) as potential indicators of personality disorder severity. For 6912 patients with a personality disorder diagnosis, we examined associations between HoNOS items relating to core personality disorder symptoms (self-harm, difficulty in interpersonal relationships, performance of occupational and social roles, and agitation and aggression) and future health service use. Compared with those with no self-harm problem, the total healthcare cost was 2.74 times higher (95% CI 1.66-4.52; P < 0.001) for individuals with severe to very severe self-harm problems. Other HoNOS items did not demonstrate clear patterns of association with service costs. Self-harm may be a robust indicator of the severity of personality disorder, but further replication work is required.

Conservation and Expansion of Transcriptional Factor Repertoire in the Fusarium oxysporum Species Complex.

The Fusarium oxysporum species complex (FOSC) includes both plant and human pathogens that cause devastating plant vascular wilt diseases and threaten public health. Each F. oxysporum genome comprises core chromosomes (CCs) for housekeeping functions and accessory chromosomes (ACs) that contribute to host-specific adaptation. This study inspects global transcription factor profiles (TFomes) and their potential roles in coordinating CC and AC functions to accomplish host-specific interactions. Remarkably, we found a clear positive correlation between the sizes of TFomes and the proteomes of an organism. With the acquisition of ACs, the FOSC TFomes were larger than the other fungal genomes included in this study. Among a total of 48 classified TF families, 14 families involved in transcription/translation regulations and cell cycle controls were highly conserved. Among the 30 FOSC expanded families, Zn2-C6 and Znf_C2H2 were most significantly expanded to 671 and 167 genes per family including well-characterized homologs of Ftf1 (Zn2-C6) and PacC (Znf_C2H2) that are involved in host-specific interactions. Manual curation of characterized TFs increased the TFome repertoires by 3% including a disordered protein Ren1. RNA-Seq revealed a steady pattern of expression for conserved TF families and specific activation for AC TFs. Functional characterization of these TFs could enhance our understanding of transcriptional regulation involved in FOSC cross-kingdom interactions, disentangle species-specific adaptation, and identify targets to combat diverse diseases caused by this group of fungal pathogens.

Chromosome-level genomes of multicellular algal sisters to land plants illuminate signaling network evolution.

The filamentous and unicellular algae of the class Zygnematophyceae are the closest algal relatives of land plants. Inferring the properties of the last common ancestor shared by these algae and land plants allows us to identify decisive traits that enabled the conquest of land by plants. We sequenced four genomes of filamentous Zygnematophyceae (three strains of Zygnema circumcarinatum and one strain of Z. cylindricum) and generated chromosome-scale assemblies for all strains of the emerging model system Z. circumcarinatum. Comparative genomic analyses reveal expanded genes for signaling cascades, environmental response, and intracellular trafficking that we associate with multicellularity. Gene family analyses suggest that Zygnematophyceae share all the major enzymes with land plants for cell wall polysaccharide synthesis, degradation, and modifications; most of the enzymes for cell wall innovations, especially for polysaccharide backbone synthesis, were gained more than 700 million years ago. In Zygnematophyceae, these enzyme families expanded, forming co-expressed modules. Transcriptomic profiling of over 19 growth conditions combined with co-expression network analyses uncover cohorts of genes that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

Conservation and Expansion of Transcriptional Factor Repertoire in the Fusarium oxysporum Species Complex.

The Fusarium oxysporum species complex (FOSC) includes both plant and human pathogens that cause devastating plant vascular wilt diseases and threaten public health. Each F. oxysporum genome comprises core chromosomes (CCs) for housekeeping functions and accessory chromosomes (ACs) that contribute to host-specific adaptation. This study inspected global transcription factor profiles (TFomes) and their potential roles in coordinating CCs and ACs functions to accomplish host-specific pathogenicity. Remarkably, we found a clear positive correlation between the sizes of TFome and proteome of an organism, and FOSC TFomes are larger due to the acquisition of ACs. Among a total of 48 classified TF families, 14 families involved in transcription/translation regulations and cell cycle controls are highly conserved. Among 30 FOSC expanded families, Zn2-C6 and Znf_C2H2 are most significantly expanded to 671 and 167 genes per family, including well-characterized homologs of Ftf1 (Zn2-C6) and PacC (Znf_C2H2) involved in host-specific interactions. Manual curation of characterized TFs increased the TFome repertoires by 3%, including a disordered protein Ren1. Expression profiles revealed a steady expression of conserved TF families and specific activation of AC TFs. Functional characterization of these TFs could enhance our understanding of transcriptional regulation involved in FOSC cross-kingdom interactions, disentangle species-specific adaptation, and identify targets to combat diverse diseases caused by this group of fungal pathogens.

Outcomes following suicidal crisis among hazardous and harmful alcohol users in the Crisis Resolution Team.

Despite associations between alcohol use and suicidal acts, little research measures prognoses of alcohol-using patients treated by Crisis Resolution Teams (CRTs), an intensive community-based intervention. We estimated the association of alcohol use amongst patients accepted following suicidal acts or ideation in four London-based Crisis Resolution Teams, with death-by-any-cause or recontact with crisis care. We analysed the electronic health records of 1615 CRT patients accepted following suicidal acts or ideation over 38 months, following STROBE guidelines. Using logistic regression we estimated the association of alcohol use (indicated by risk-assessment, AUDIT, or ICD-10 diagnosis) with death-or-recontact at (i) 30-days and (ii) 1-year after treatment start, adjusted for age, sex, ethnicity, psychiatric diagnosis, and severity of need. Hazardous, harmful, or dependent drinking was identified in 270 cases at baseline (16.7%); 73 (4.5%) were alcohol dependent. By 1-year, 622 patients (38.5%) had recontacted crisis care or died. After adjustment, alcohol use at a hazardous, harmful, or dependent level was not associated with increased odds of death-or-recontact at 30-days (AOR 1.17, 95%CI 0.73, 1.88) or 1-year (AOR 1.17, 95%CI 0.85, 1.60). Patients with hazardous, harmful, and dependent alcohol use are a small proportion of CRT patients, despite being more commonly encountered in emergency settings from which patients may be referred to CRTs, indicating a potential gap in provision. Those who are included in CRTs are not at increased risk of death-or-recontact within 1 year of treatment, suggesting that their inclusion can work, at least in a sample with predominantly hazardous or harmful alcohol use.

Mental health problems and admissions to hospital for accidents and injuries in the UK military: A data linkage study.

PURPOSE: Accidents are the most common cause of death among UK military personnel. It is a common misconception in the general public that accidental injuries are always the result of random events, however research suggests that mental health problems and the increased levels of risky behaviour in military personnel may play a role. The objective of this study was to further our understanding of injuries and deaths not related to deployment by examining the associations of mental health, alcohol misuse and smoking with inpatient admission to hospital for accidents and injuries, and attendance to accident and emergency (A&E) departments. METHODS: Data on all hospital admissions for accidents and injuries and A&E attendance at NHS hospitals in England, Scotland and Wales were linked to data on self-reported mental health problems, alcohol misuse and smoking from a large, representative UK military cohort of serving and ex-serving personnel (n = 8,602). Logistic regression was used to examine the associations between having a hospital admission for an accident or injury with self-reported mental health problems, alcohol misuse and smoking. Cox proportional-hazards regression was then conducted to assess the associations of mental health problems, alcohol misuse and smoking with time to hospital admission for an accident or injury. Finally, negative binomial regression was used to examine associations between the number of A&E attendances with mental health problems, alcohol misuse and smoking. RESULTS: Personnel reporting symptoms of common mental disorder (CMD) or probable post-traumatic stress disorder (PTSD) were more likely to have an admission to hospital for an accident or injury (fully adjusted odds ratio 1.39, 95% confidence interval [CI] 1.05-1.84), than those who did not report these symptoms, and also had more attendances to A&E (fully adjusted incidence rate ratio [IRR] 1.32, 95% CI 1.16-1.51). A&E attendances were also more common in personnel who were smokers (fully adjusted IRR 1.21, 95% CI 1.09-1.35) following adjustment for demographic, military and health characteristics. CONCLUSIONS: The findings suggest that accidents and injuries among military personnel are not always random events and that there are health and behavioural factors, including poor mental health and smoking, which are associated (with small effect sizes) with an increased risk of being involved in an accident. Clinicians treating individuals attending hospital after an accident should consider their healthcare needs holistically, including issues related to mental health and health damaging behaviours.

Ethnic inequalities in involuntary admission under the Mental Health Act: an exploration of mediation effects of clinical care prior to the first admission.

BACKGROUND: Studies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission. AIMS: This study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care. METHOD: In this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association. RESULTS: Compared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission. CONCLUSIONS: Ethnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.

Clinical correlates of early onset antipsychotic treatment resistance.

BACKGROUND: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. AIM: This study investigates sociodemographic and clinical correlates of early onset of TRS. METHOD: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. RESULTS: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). CONCLUSION: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Prevalence and Correlates of Obsessive-Compulsive Symptoms in Individuals With Schizophrenia, Schizoaffective Disorder, or Bipolar Disorder.

Objective: Although frequently reported in psychosis, obsessive-compulsive symptoms (OCS) are often not recognized and thus undertreated. We aimed to estimate the prevalence of OCS and obsessive-compulsive disorder (OCD) in patients with schizophrenia, schizoaffective disorder, or bipolar disorder in clinical records and identify clinical associations of OCS co-occurrence.Methods: Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre case register. The study population was restricted to individuals diagnosed with schizophrenia (ICD F20.x), schizoaffective disorder (ICD F25.x), or bipolar disorder (ICD F31.x) between 2007 and 2015. OCS and OCD were ascertained from structural fields and via Natural Language Processing software applied to free-text records. Clinical characteristics were obtained from Health of the Nation Outcome Scales for the analyses on associations between clinical characteristics and OCS/OCD status using logistic regressions with confounders considered.Results: 22,551 cases of schizophrenia, schizoaffective disorder, or bipolar disorder were identified in the observation window. Among these, 5,179 (24.0%) were identified as having OCS (including an OCD diagnosis) and 2,574 (11.9%) specifically with comorbid OCD. OCS/OCD was associated with an increased likelihood of recorded aggressive behavior (OR = 1.18; 95% CI, 1.10-1.26), cognitive problems (OR = 1.21; 95% CI, 1.13-1.30), hallucinations and delusions (OR = 1.11; 95% CI, 1.04-1.20), and physical problems (OR = 1.17; 95% CI, 1.09-1.26).Conclusions: OCS and OCD are frequently recorded for patients with schizophrenia, schizoaffective disorder, and bipolar disorder and are associated with more severe psychiatric clinical characteristics. Automated information extraction tools hold potential to improve recognition and treatment of co-occurring OCS/OCD for psychosis.

A predictor model of treatment resistance in schizophrenia using data from electronic health records.

OBJECTIVES: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. METHODS: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. RESULTS: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. CONCLUSIONS: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

Ethnic disparities in clozapine prescription for service-users with schizophrenia-spectrum disorders: a systematic review.

Clozapine is the only licenced medication for treating treatment-resistant schizophrenia. Previous studies have suggested unequal rates of clozapine treatment by ethnicity among individuals with schizophrenia-spectrum disorders. One previous review has investigated this topic but was restricted to studies from the USA. This current review aims to synthesise the international literature regarding ethnic disparities in clozapine prescription amongst individuals with schizophrenia-spectrum disorders. We searched CINAHL, PubMed, Medline, Embase, APA PsycINFO and Open Grey and reviewed studies reporting on the proportion of service-users prescribed clozapine separately for different ethnic groups, in individuals with a primary diagnosis of schizophrenia or any schizophrenia-spectrum disorders. A narrative synthesis was conducted to integrate information from included studies. The review was registered in PROSPERO (Number: CRD42020221731). From 24 studies, there is strong, consistent evidence that Black and Hispanic service-users in the UK and the USA are significantly less likely to receive clozapine than White/Caucasian service-users after controlling for multiple demographic and clinical potential confounders. In New Zealand, Maori service-users were reported to be more likely to receive clozapine than those of White/European ethnicity. There is mixed evidence regarding Asian service-users in the UK. The mentioned disparities were observed in studies with TRS and non-TRS cohorts. The results imply that access to clozapine treatment varies among ethnic groups. These findings raise an ethical concern as they suggest a compromise of the standards of care in schizophrenia treatment practices. Interventions are needed to reduce clozapine prescribing disparities among ethnic communities.

Autism spectrum disorders as a risk factor for adolescent self-harm: a retrospective cohort study of 113,286 young people in the UK.

BACKGROUND: Individuals with autism spectrum disorder (ASD) are at particularly high risk of suicide and suicide attempts. Presentation to a hospital with self-harm is one of the strongest risk factors for later suicide. We describe the use of a novel data linkage between routinely collected education data and child and adolescent mental health data to examine whether adolescents with ASD are at higher risk than the general population of presenting to emergency care with self-harm. METHODS: A retrospective cohort study was conducted on the population aged 11-17 resident in four South London boroughs between January 2009 and March 2013, attending state secondary schools, identified in the National Pupil Database (NPD). Exposure data on ASD status were derived from the NPD. We used Cox regression to model time to first self-harm presentation to the Emergency Department (ED). RESULTS: One thousand twenty adolescents presented to the ED with self-harm, and 763 matched to the NPD. The sample for analysis included 113,286 adolescents (2.2% with ASD). For boys only, there was an increased risk of self-harm associated with ASD (adjusted hazard ratio 2·79, 95% CI 1·40-5·57, P<0·01). Several other factors including school absence, exclusion from school and having been in foster care were also associated with a higher risk of self-harm. CONCLUSIONS: This study provides evidence that ASD in boys, and other educational, social and clinical factors, are risk factors for emergency presentation with self-harm in adolescents. These findings are an important step in developing early recognition and prevention programmes.

Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.

PURPOSE: Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder. METHODS: A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use. RESULTS: Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine. CONCLUSION: Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.

Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine.

BACKGROUND: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment. METHODS: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale. RESULTS: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data. CONCLUSIONS: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.

COVID-related hospitalization, intensive care treatment, and all-cause mortality in patients with psychosis and treated with clozapine.

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this.

Ecological generalism drives hyperdiversity of secondary metabolite gene clusters in xylarialean endophytes.

Although secondary metabolites are typically associated with competitive or pathogenic interactions, the high bioactivity of endophytic fungi in the Xylariales, coupled with their abundance and broad host ranges spanning all lineages of land plants and lichens, suggests that enhanced secondary metabolism might facilitate symbioses with phylogenetically diverse hosts. Here, we examined secondary metabolite gene clusters (SMGCs) across 96 Xylariales genomes in two clades (Xylariaceae s.l. and Hypoxylaceae), including 88 newly sequenced genomes of endophytes and closely related saprotrophs and pathogens. We paired genomic data with extensive metadata on endophyte hosts and substrates, enabling us to examine genomic factors related to the breadth of symbiotic interactions and ecological roles. All genomes contain hyperabundant SMGCs; however, Xylariaceae have increased numbers of gene duplications, horizontal gene transfers (HGTs) and SMGCs. Enhanced metabolic diversity of endophytes is associated with a greater diversity of hosts and increased capacity for lignocellulose decomposition. Our results suggest that, as host and substrate generalists, Xylariaceae endophytes experience greater selection to diversify SMGCs compared with more ecologically specialised Hypoxylaceae species. Overall, our results provide new evidence that SMGCs may facilitate symbiosis with phylogenetically diverse hosts, highlighting the importance of microbial symbioses to drive fungal metabolic diversity.

Genome, transcriptome and secretome analyses of the antagonistic, yeast-like fungus Aureobasidium pullulans to identify potential biocontrol genes.

Aureobasidium pullulans is an extremotolerant, cosmopolitan yeast-like fungus that successfully colonises vastly different ecological niches. The species is widely used in biotechnology and successfully applied as a commercial biocontrol agent against postharvest diseases and fireblight. However, the exact mechanisms that are responsible for its antagonistic activity against diverse plant pathogens are not known at the molecular level. Thus, it is difficult to optimise and improve the biocontrol applications of this species. As a foundation for elucidating biocontrol mechanisms, we have de novo assembled a high-quality reference genome of a strongly antagonistic A. pullulans strain, performed dual RNA-seq experiments, and analysed proteins secreted during the interaction with the plant pathogen Fusarium oxysporum. Based on the genome annotation, potential biocontrol genes were predicted to encode secreted hydrolases or to be part of secondary metabolite clusters (e.g., NRPS-like, NRPS, T1PKS, terpene, and ß-lactone clusters). Transcriptome and secretome analyses defined a subset of 79 A. pullulans genes (among the 10,925 annotated genes) that were transcriptionally upregulated or exclusively detected at the protein level during the competition with F. oxysporum. These potential biocontrol genes comprised predicted secreted hydrolases such as glycosylases, esterases, and proteases, as well as genes encoding enzymes, which are predicted to be involved in the synthesis of secondary metabolites. This study highlights the value of a sequential approach starting with genome mining and consecutive transcriptome and secretome analyses in order to identify a limited number of potential target genes for detailed, functional analyses.