How TikTok is being used to talk about abortion post-Roe: A content analysis of the most liked abortion TikToks.

OBJECTIVES: Access to information about abortion is essential for ensuring reproductive autonomy, particularly post-Roe. TikTok, a popular video-sharing application, may be a source of information about abortion, yet little is known about the tone and content of such videos. To fill this gap, we analyze the most liked abortion videos on TikTok three months following the U.S. Supreme Court decision Dobbs v. Jackson Women's Health Organization. STUDY DESIGN: We downloaded the top 200 most liked, publicly available TikTok videos when searching "abortion" on September 26, 2022 and recorded and summarized key video characteristics. We then qualitatively analyzed for content, tone, and common themes. RESULTS: The top 200 most liked TikTok videos collectively had approximately 164 million likes, nearly 10 million shares, and 4 million comments. Most videos expressed support for abortion and presented information that was political or personal in nature. Only two videos contained health information about obtaining or completing an abortion, and only five videos featured or were created by a medical provider. CONCLUSIONS: Findings reveal the far reach of TikTok, which underscores the importance of analyzing online sources of information about abortion. However, our mixed-methods analysis indicates that the most liked TikToks are a source of abortion news, political opinion, personal stories, and debate rather than a source of health information for abortion seekers. IMPLICATIONS: Our analysis finds that the top 200 most liked TikTok videos three months post-Dobbs are primarily political in nature. Relatively few videos provided practical information about accessing abortion care, presenting an opportunity for healthcare providers, public health advocates, and activists to improve access and awareness of new pathways to care. The most popular TikTok videos appear to disseminate news and political information rather than health information about abortion.

Support for criminalization of self-managed abortion (SMA): A national representative survey.

OBJECTIVE: Since the U.S. Supreme Court eliminated the federal right to abortion, there is a heightened need to understand public opinion about the criminalization of people who attempt to end their pregnancies outside the formal healthcare setting, referred to as self-managed abortion (SMA). We assessed U.S. attitudes about whether three forms of SMA should be legal, reported or punished: 1) using abortion pills obtained outside the healthcare system, 2) using other medications, drugs, herbs, or by drinking alcohol, and 3) using traumatic methods (inserting an object in their body or hitting their stomach). METHODS: From December 2021 to January 2022, we administered a national probability-based online survey to English- and Spanish-speaking people assigned female (AFAB, ages 15-49) or male at birth (AMAB, ages 18-49) regarding their attitudes about criminalizing SMA, using Ipsos' KnowledgePanel. We estimated weighted proportions and conducted multivariable regression analyses to identify characteristics associated with support for SMA legality and punishment (reporting to authorities, paying a fine or going to jail). RESULTS: A total of 7,016 AFAB and 360 AMAB completed the survey. People were less likely (p < .05) to agree that SMA using abortion pills should be illegal (34% of AFAB and 43% of AMAB) than other forms of SMA (36-48%), although over one-fifth were unsure (AFAB, 20-23% and AMAB, 24-27%). People were less likely to agree SMA using abortion pills should be criminalized than SMA using other drugs, medications, herbs, alcohol or by using traumatic methods. In multivariable analyses, AMAB and Christian religion were associated with agreeing that SMA using abortion pills should be illegal; people who identified as Hispanic/Latinx ethnicity and experienced medical mistreatment were less likely to agree SMA with medication abortion pills should be illegal. CONCLUSIONS: Public support for criminalizing SMA is complex and varied by SMA method and form of punishment.

The Role of Telehealth in Promoting Equitable Abortion Access in the United States: Spatial Analysis.

BACKGROUND: Even preceding the Supreme Court's 2022 Dobbs v. Jackson Women's Health Organization decision, patients in the United States faced exceptional barriers to reach abortion providers. Abortion restrictions disproportionately limited abortion access among people of color, young people, and those living on low incomes. Presently, clinics in states where abortion remains legal are experiencing an influx of out-of-state patients and wait times for in-person appointments are increasing. Direct-to-patient telehealth for abortion care has expanded since its introduction in the United States in 2020. However, the role of this telehealth model in addressing geographic barriers to and inequities in abortion access remains unclear. OBJECTIVE: We sought to examine the amount of travel that patients averted by using telehealth for abortion care, and the role of telehealth in mitigating inequities in abortion access by race or ethnicity, age, pregnancy duration, socioeconomic status, rural residence, and distance to a facility. METHODS: We used geospatial analyses and data from patients in the California Home Abortion by Telehealth Study, residing in 31 states and Washington DC, who obtained telehealth abortion care at 1 of 3 virtual abortion clinics. We used patients' residential ZIP code data and data from US abortion facility locations to document the round-trip driving distance in miles, driving time, and public transit time to the nearest abortion facility that patients averted by using telehealth abortion services from April 2021 to January 2022, before the Dobbs decision. We used binomial regression to assess whether patients reported that telehealth was more likely to make it possible to access a timely abortion among patients of color, those experiencing food insecurity, younger patients, those with longer pregnancy durations, rural patients, and those residing further from their closest abortion facility. RESULTS: The 6027 patients averted a median of 10 (IQR 5-26) miles and 25 (IQR 14-46) minutes of round-trip driving, and 1 hour 25 minutes (IQR 46 minutes to 2 hours 30 minutes) of round-trip public transit time. Among a subsample of 1586 patients surveyed, 43% (n=683) reported that telehealth made it possible to obtain timely abortion care. Telehealth was most likely to make it possible to have a timely abortion for younger patients (prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) for patients younger than 25 years of age compared to those 35 years of age or older), rural patients (PR 1.4, 95% CI 1.2-1.6), those experiencing food insecurity (PR 1.3, 95% CI 1.1-1.4), and those who averted over 100 miles of driving to their closest abortion facility (PR 1.6, 95% CI 1.3-1.9). CONCLUSIONS: These findings support the role of telehealth in reducing abortion-related travel barriers in states where abortion remains legal, especially among patient populations who already face structural barriers to abortion care. Restrictions on telehealth abortion threaten health equity.

Self-removal of long-acting reversible contraception: A content analysis of YouTube videos.

OBJECTIVE: To explore publicly available information about the self-removal of long-acting reversible contraception (LARC) on a popular video-sharing website. STUDY DESIGN: We conducted a comprehensive keyword search of YouTube videos related to self-removal of LARC-namely intrauterine devices and implants. We analyzed video content to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. RESULTS: Our keyword search identified 58 videos that met the criteria for inclusion, including 48 videos that featured individuals who removed an intrauterine device and 10 who removed an implant. Collectively, videos had over 4 million views. We identified most video creators as white (53%), 31% as Black, and 14% as Latinx. Users were motivated to remove their own device by both preferences and barriers to formal care. Most individuals in our sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Reasons for LARC discontinuation included negative side effects, fear of potential side effects, and desire for pregnancy. CONCLUSION: This study builds upon prior research by describing publicly available information about LARC self-removal. The over representation of Black women in our sample may reflect a higher prevalence of LARC self-removal among this population. Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. IMPLICATIONS: Prior to LARC insertion, patients should be made aware of any financial requirements for discontinuation. Provider counseling for self-removal at the time of insertion will likely minimize health risks and affirm patient reproductive autonomy.

Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non-small cell lung cancer.

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking-in part due to the difficulty in assessing migration using high-throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the 'identification of Migration control genes by differential Expression'. MigExpress exploits the combination of in-depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration-associated genes by their differential expression in slow- versus fast-migrating cells. We applied MigExpress to investigate non-small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration.

"It makes it more real": Examining ambiguous fetal meanings in abortion care.

The role of fetal development in abortion work is unresolved, mirroring a broader cultural ambivalence regarding the fetus. The collective, cultural notion of fetuses tends to lie on a dichotomy between "clump of cells" and "baby," with little public attention to the realities of fetal development during all stages of pregnancy. This tension is exacerbated by an absence of medically accurate images of aborted fetal tissue available to lay audiences. In this paper, we examine how independent abortion providers manage contradictory messages surrounding the fetus when providing patient-centered pregnancy tissue viewing (PCV). More specifically, we investigate how providers navigate public and private understandings of the fetus in their healthcare provision amidst a void of nuanced fetal imagery. Through interviews with 25 independent abortion providers in the United States, we analyze the discursive framings providers employ to make sense of the fetus and provision of PCV. Using a symbolic interactionism framework, we grouped results into three overarching themes: tensions in language, the impact of gestation as de- or re-stigmatizing, and looking as "making it more real." Our findings support the notion that the fetus is largely socially constructed, mutable, and variant across individuals, context, and time; our findings also highlight abortion providers' ability to hold nuanced and sometimes conflicting thoughts and feelings about fetuses while providing patient-centered care. This study addresses a largely overlooked practice within medical sociology and furthers our understanding of how cultural narratives shape the provision and meanings of patient-centered care, the professional socialization of healthcare workers, and the patient-provider interaction.

The Circular RNA Landscape of Non-Small Cell Lung Cancer Cells.

The class of circular RNA (circRNA) is characterized by head-to-tail bonds between exons formed by backsplicing. Here, we provide a resource of circRNA expression in a comprehensive panel of 60 lung cancer and non-transformed cell lines (FL3C dataset). RNA sequencing after depletion of ribosomal RNA quantified the expression of circRNA and linear RNA. We detected 148,811 circular RNAs quantified by 2.8 million backsplicing reads originating from 12,251 genes. The number of identified circRNAs was markedly higher using rRNA depletion compared to public polyA-enriched RNA-seq datasets. CircRNAs almost never started in the first exon nor ended in the last exon and started more frequently in earlier exons. Most circRNAs showed high cell line specificity and correlated positively with their linear RNA counterpart. Known cancer genes produced more circRNAs than non-cancer genes. Subsets of circRNAs correlated with cell proliferation, histological subtype or genotype. CircTNFRSF21 was translated crossing the backsplice site in two different reading frames. Overexpression of circPVT1, circERBB2, circHIPK3, circCCNB1, circSMAD2, circTNFRSF21 and circKIF5B significantly increased colony formation. In conclusion, our data provide a comprehensive map of circRNA expression in lung cancer cells and global patterns of circRNA production as a useful resource for future research into lung cancer circRNAs.

The option to look: patient-centred pregnancy tissue viewing at independent abortion clinics in the United States.

Abortion providers' approaches to patient-centred pregnancy tissue viewing (PCV) - when a patient requests to see their products of conception - is understudied in abortion care. This mixed-method study aimed to identify: (1) if, when, and how PCV is facilitated at US independent abortion clinics; (2) how staff are trained to offer viewing; and (3) provider experiences facilitating PCV. We surveyed administrators from 22 independent abortion clinics affiliated with the Abortion Care Network about their PCV practices and then completed in-depth semi-structured interviews with 25 providers to better understand their experiences facilitating PCV. Results indicate that most of the clinics that provide PCV do so by patient request. A variety of providers facilitate viewing, including counsellors, educators, physicians, nurses, and medical assistants. Timing, viewing location, and staff training vary by facility. Benefits of and barriers to PCV emerged through three themes: (1) patient-centred care; (2) misinformation about fetal tissue; and (3) personal navigations as providers. Providers and administrators report PCV aligns with their patient-centred clinic missions and offers patients opportunities for choice, closure, and access to information. Yet, anti-abortion misinformation about fetal tissue impacts the ways providers must navigate complex conversations about PCV professionally and personally. Clinic resources and concern about adverse patient reactions to identifiable fetal parts present barriers to offering viewing. Understanding providers' experiences and approaches to PCV is an important first step to developing quality practices that can be shared across clinics. The findings of this study support the need for more research and training on PCV in abortion care.

Influenza A Virus Induces Autophagosomal Targeting of Ribosomal Proteins.

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three human epithelial cell lines derived from human lung carcinomas: A549, Calu-1 and NCI-H1299. As a common response, the type I interferon pathway was up-regulated upon infection. Interestingly, influenza A virus infection led to numerous cell line-specific responses affecting both protein abundance as well as subcellular localization. In A549 cells, the vesicular compartment appeared expanded after virus infection. The composition of autophagsomes was altered by targeting of ribosomes, viral mRNA and proteins to these double membrane vesicles. Thus, autophagy may support viral protein translation by promoting the clustering of the respective molecular machinery in autophagosomes in a cell line-dependent manner.

LINC00261 and the Adjacent Gene FOXA2 Are Epithelial Markers and Are Suppressed during Lung Cancer Tumorigenesis and Progression.

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated. LINC00261 as well as FOXA2 negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFß. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high LINC00261/FOXA2 expression to an epithelial gene signature. Furthermore, higher expression of the LINC00261/FOXA2 locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish LINC00261 and FOXA2 as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.

Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.

Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.

The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior.

Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D culture systems. Interestingly, these effects were mainly observed in RAS mutant cancer cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1 in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1 activates NF-κB signaling and promotes cell cycle progression. Using proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung colonization in vivo and that RIOK1 is overexpressed in different subtypes of human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential therapeutic target, especially in RAS-driven cancers.

Degradation of protein translation machinery by amino acid starvation-induced macroautophagy.

Macroautophagy is regarded as a nonspecific bulk degradation process of cytoplasmic material within the lysosome. However, the process has mainly been studied by nonspecific bulk degradation assays using radiolabeling. In the present study we monitor protein turnover and degradation by global, unbiased approaches relying on quantitative mass spectrometry-based proteomics. Macroautophagy is induced by rapamycin treatment, and by amino acid and glucose starvation in differentially, metabolically labeled cells. Protein dynamics are linked to image-based models of autophagosome turnover. Depending on the inducing stimulus, protein as well as organelle turnover differ. Amino acid starvation-induced macroautophagy leads to selective degradation of proteins important for protein translation. Thus, protein dynamics reflect cellular conditions in the respective treatment indicating stimulus-specific pathways in stress-induced macroautophagy.

Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses.

The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to decreased endocytosis and degradation. Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8(+) T cell responses more efficiently in vitro and in vivo. During viral infections, lack of Atg5 results in enhanced influenza- and LCMV-specific CD8(+) T cell responses in vivo. Elevated influenza-specific CD8(+) T cell responses are associated with better immune control of this infection. Thus, the macroautophagy machinery orchestrates T cell immunity by supporting MHC class II but compromises MHC class I restricted antigen presentation.

Autophagosomal proteome analysis by protein correlation profiling-SILAC.

Autophagy is one of the two major degradation pathways within eukaryotic cells. Nevertheless, little is known about the protein composition of autophagosomes, the vesicles shuttling proteins to lysosomes for degradation. Protein correlation profiling in combination with stable isotope labeling by amino acids in cell culture is a stringent method to investigate the dynamics of the autophagosomal proteome. It enables the discrimination between autophagosomal and co-purifying proteins identifying organellar candidate proteins for further investigation.

Characterization of early autophagy signaling by quantitative phosphoproteomics.

Under conditions of nutrient shortage autophagy is the primary cellular mechanism ensuring availability of substrates for continuous biosynthesis. Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon induction of autophagy with both treatments affecting widely different cellular processes. The identification of dynamic phosphorylation already after 2 min demonstrates that the earliest events in autophagy signaling occur rapidly after induction. The data was subjected to extensive bioinformatics analysis revealing regulated phosphorylation sites on proteins involved in a wide range of cellular processes and an impact of the treatments on the kinome. To approach the potential function of the identified phosphorylation sites we performed a screen for MAP1LC3-interacting proteins and identified a group of binding partners exhibiting dynamic phosphorylation patterns. The data presented here provide a valuable resource on phosphorylation events underlying early autophagy induction.

Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing.

Antigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.

Friend or food: different cues to the autophagosomal proteome.

A hallmark of macroautophagy is the formation of autophagosomes, double-membrane vesicles that enwrap cellular components destined for lysosomal degradation. We examined autophagosomal protein dynamics under various inducing stimuli using a comprehensive mass spectrometry-based proteomics approach in combination with functional studies in yeast and human cell cultures. Time frame and stimuli type influenced the autophagosome proteome, underlining the dynamic constitution of the organelle. We identified both a core set of proteins always localizing to autophagosomes and stimulus-dependent components that will serve as a resource for further characterization of the autophagosomal machinery and cargo selection. Among the core proteins were newly discovered autophagy regulators found to be conserved from yeast to humans, as well as the proteasome.

Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens.

Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome-associated proteins were dependent on stimulus, but a core set of proteins was stimulus-independent. Remarkably, proteasomal proteins were abundant among the stimulus-independent common autophagosome-associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome-associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection.

The degradative inventory of the cell: proteomic insights.

SIGNIFICANCE: Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES: Technical advances in the field of quantitative mass spectrometry (MS)-based proteomics allow for detailed investigations of protein degradation dynamics and identifications of responsible protein-protein interaction networks enabling a systematic analysis of the degradative inventory of the cell and its underlying molecular mechanisms. CRITICAL ISSUES: In the current review we outline recent technical advances and their limitations in MS-based proteomics and discuss their use for the analysis of protein dynamics involved in degradation processes. FUTURE DIRECTIONS: In the next years the analysis of crosstalk between different posttranslational modifications (PTMs) will be a major focus of MS-based proteomics studies. Increasing evidence highlights the complexity of PTMs with positive and negative feedbacks being discovered. In this regard, the generation of absolute quantitative proteomic data will be essential for theoretical scientists to construct predictive network models that constitute a valuable tool for fast hypothesis testing and for explaining underlying molecular mechanisms.