A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.

Background In the absence of a vaccine or effective treatment for COVID-19, countries have adopted nonpharmaceutical interventions (NPIs) such as social distancing and full lockdown. An objective and quantitative means of passively monitoring the impact and response of these interventions at a local level is needed. Objective We aim to explore the utility of the recently developed open-source mobile health platform Remote Assessment of Disease and Relapse (RADAR)–base as a toolbox to rapidly test the effect and response to NPIs intended to limit the spread of COVID-19. Methods We analyzed data extracted from smartphone and wearable devices, and managed by the RADAR-base from 1062 participants recruited in Italy, Spain, Denmark, the United Kingdom, and the Netherlands. We derived nine features on a daily basis including time spent at home, maximum distance travelled from home, the maximum number of Bluetooth-enabled nearby devices (as a proxy for physical distancing), step count, average heart rate, sleep duration, bedtime, phone unlock duration, and social app use duration. We performed Kruskal-Wallis tests followed by post hoc Dunn tests to assess differences in these features among baseline, prelockdown, and during lockdown periods. We also studied behavioral differences by age, gender, BMI, and educational background. Results We were able to quantify expected changes in time spent at home, distance travelled, and the number of nearby Bluetooth-enabled devices between prelockdown and during lockdown periods (P<.001 for all five countries). We saw reduced sociality as measured through mobility features and increased virtual sociality through phone use. People were more active on their phones (P<.001 for Italy, Spain, and the United Kingdom), spending more time using social media apps (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), particularly around major news events. Furthermore, participants had a lower heart rate (P<.001 for Italy and Spain; P=.02 for Denmark), went to bed later (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), and slept more (P<.001 for Italy, Spain, and the United Kingdom). We also found that young people had longer homestay than older people during the lockdown and fewer daily steps. Although there was no significant difference between the high and low BMI groups in time spent at home, the low BMI group walked more. Conclusions RADAR-base, a freely deployable data collection platform leveraging data from wearables and mobile technologies, can be used to rapidly quantify and provide a holistic view of behavioral changes in response to public health interventions as a result of infectious outbreaks such as COVID-19. RADAR-base may be a viable approach to implementing an early warning system for passively assessing the local compliance to interventions in epidemics and pandemics, and could help countries ease out of lockdown.

Analysis of incomplete data is a big challenge when integrating large-scale brain imaging datasets from different imaging modalities. In the Alzheimer’s Disease Neuroimaging Initiative (ADNI), for example, over half of the subjects lack cerebrospinal fluid (CSF) measurements; an independent half of the subjects do not have fluorodeoxyglucose positron emission tomography (FDG-PET) scans; many lack proteomics measurements. Traditionally, subjects with missing measures are discarded, resulting in a severe loss of available information. In this paper, we address this problem by proposing an incomplete Multi-Source Feature (iMSF) learning method where all the samples (with at least one available data source) can be used. To illustrate the proposed approach, we classify patients from the ADNI study into groups with Alzheimer’s disease (AD), mild cognitive impairment (MCI) and normal controls, based on the multi-modality data. At baseline, ADNI’s 780 participants (172 AD, 397 MCI, 211 NC), have at least one of four data types: magnetic resonance imaging (MRI), FDG-PET, CSF and proteomics. These data are used to test our algorithm. Depending on the problem being solved, we divide our samples according to the availability of data sources, and we learn shared sets of features with state-of-the-art sparse learning methods. To build a practical and robust system, we construct a classifier ensemble by combining our method with four other methods for missing value estimation. Comprehensive experiments with various parameters show that our proposed iMSF method and the ensemble model yield stable and promising results.

Background There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes. Methods RADAR-MDD is a multi-site prospective cohort study, aiming to recruit 600 participants with a history of depressive disorder across three sites: London, Amsterdam and Barcelona. Participants will be asked to wear a wrist-worn activity tracker and download several apps onto their smartphones. These apps will be used to either collect data passively from existing smartphone sensors, or to deliver questionnaires, cognitive tasks, and speech assessments. The wearable device, smartphone sensors and questionnaires will collect data for up to 2-years about participants’ sleep, physical activity, stress, mood, sociability, speech patterns, and cognitive function. The primary outcome of interest is MDD relapse, defined via the Inventory of Depressive Symptomatology- Self-Report questionnaire (IDS-SR) and the World Health Organisation’s self-reported Composite International Diagnostic Interview (CIDI-SF). Discussion This study aims to provide insight into the early predictors of major depressive relapse, measured unobtrusively via RMT. If found to be acceptable to patients and other key stakeholders and able to provide clinically useful information predictive of future deterioration, RMT has potential to change the way in which depression and other long-term conditions are measured and managed. Electronic supplementary material The online version of this article (10.1186/s12888-019-2049-z) contains supplementary material, which is available to authorized users.