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13. Southern Ocean warming and its climatic impacts

Author

Wenju Cai, Libao Gao, Yiyong Luo, Xichen Li, Xiaotong Zheng, Xuebin Zhang, Xuhua Cheng, Fan Jia, Ariaan Purich, Agus Santoso, Yan Du, David M. Holland, Jia-Rui Shi, Baoqiang Xiang, and Shang-Ping Xie

Subjects
Multidisciplinary
Published
2023

14. Fast and Slow Responses of the Tropical Pacific to Radiative Forcing in Northern High Latitudes

Author

Hung-Yi Tseng, Yen-Ting Hwang, Shang-Ping Xie, Yu-Heng Tseng, Sarah M. Kang, Matthew T. Luongo, and Ian Eisenman

Subjects
Atmospheric Science
Abstract

This study investigates the transient evolution of tropical Pacific sea surface temperature (SST) responses to a constant northern high latitude solar heating in fully coupled CESM 1.2. The study identifies two stages through multiple ensemble runs. (1) In the first three years, a hemispherically asymmetric pattern emerges, caused by air-sea interactions associated with the anomalous cross-equatorial Hadley Cell. The northern tropics experience warming, blocked north of the equator by the intertropical convergence zone. The southeast Pacific cooling reaches the equatorial region and is amplified by the equatorial Ekman divergence. (2) Within a decade, the equatorial cooling is replaced by warming in the eastern equatorial basin. The anomalous warming that appears faster than the timescales of the oceanic ventilation is attributed to anomalous meridional heat convergence and weakening of the northern subtropical cell. Our findings highlight the influence of ocean dynamics on the temporal and spatial evolution of tropical SST response to hemispherically asymmetric heating. The initial cooling caused by Ekman divergence delays the arrival of slow warming, while initial wind and temperature anomalies set the stage for the weakening of the subtropical cell. The results have important implications for understanding the evolution of tropical SST patterns in observational records and future climate change simulations, as they show strong interhemispheric temperature asymmetry in the extratropics.

Published
2023

15. Spatial and seasonal variations of sea surface temperature threshold for tropical convection

Author

Shineng Hu, Shang-Ping Xie, Richard Seager, and Mark A. Cane

Subjects
Atmospheric Science
Abstract

Tropical rainfall variations are of direct societal relevance and drive climate variations worldwide via teleconnections. The convective rainfall tends to occur when sea surface temperature (SST) exceeds a threshold, SSTthr, usually taken to be constant in time and space. We analyze 40-year monthly observations and find that SSTthr varies by up to 4°C in space and with season. Based on local convective instability, we develop a quantitative theory that largely explains the SSTthr variations using the climatological state of the tropical atmosphere. Although it is often assumed that spatial variations of tropical upper tropospheric temperature are small and can be neglected, it is shown that lower climatological values favor a lower SSTthr. Similarly, a small increase in climatological surface relative humidity also leads to a decrease in SSTthr as does a lower climatological air-sea temperature difference. Consequently, efforts to understand and predict natural or forced variations in tropical rainfall must account for, in addition to SST, the temperatures aloft and the near surface humidity and temperature and requires improved understanding of what controls their distribution in space and time.

Published
2023

16. Enhanced ENSO-Unrelated Summer Variability in the Indo–Western Pacific under Global Warming

Author

Chuan-Yang Wang, Xiao-Tong Zheng, and Shang-Ping Xie

Subjects
Atmospheric Science
Abstract

El Niño–Southern Oscillation (ENSO) is an important but not the only source of interannual variability over the Indo–western Pacific. Non-ENSO forced variability in the region has received recent attention because of the implications for rainy-season prediction. Using a 35-member CESM1 Large Ensemble (CESM-LE) and 30 CMIP6 models, this study shows that the ensemble means project intensified interannual variability for precipitation, low-level winds, and sea level pressure under global warming, associated with the enhanced large-scale anomalous anticyclone (AAC) over the tropical northwestern (NW) Pacific after the ENSO signal is removed. A decomposition based on the column water vapor budget reveals that enhanced precipitation variability is due to the increased background specific humidity. The resultant anomalous diabatic heating intensifies the AAC, which further strengthens the precipitation anomalies. Over the tropical NW Pacific, the wind-induced evaporative cooling on the southeastern flank of the AAC is countered by the increased shortwave radiation due to the strengthened precipitation reduction. Tropospheric temperature anomalies in the ensemble means show no significant change, suggesting no apparent change of the interbasin positive feedback between the AAC and northern Indian Ocean SST. Intermodel analysis based on CMIP6 reveals that models with a larger increase in ENSO-unrelated precipitation variability over the NW Pacific are associated with stronger background warming in the eastern equatorial Pacific, due to the modulated Walker and Hadley circulations.

Published
2023

17. Indonesian Throughflow Slowdown under Global Warming: Remote AMOC Effect versus Regional Surface Forcing

Author

Qihua Peng, Shang-Ping Xie, Rui Xin Huang, Weiqiang Wang, Tingting Zu, and Dongxiao Wang

Subjects
Atmospheric Science
Abstract

The Indonesian Throughflow (ITF) is projected to slow down under anthropogenic warming. Several mechanisms—some mutually conflicting—have been proposed but the detailed processes causing this slowdown remain unclear. By turning on/off buoyancy and wind forcings globally and in key regions, this study investigates the dynamical adjustments underlying the centennial ITF slowdown in the global oceans and climate models. Our results show that the projected weakened ITF transport in the top 1500 m is dominated by remote anomalous buoyancy forcing in the North Atlantic Ocean. Specifically, surface freshening and warming over the North Atlantic Ocean slow the Atlantic meridional overturning circulation (AMOC), and the resultant dynamic signals propagate through the coastal-equatorial waveguide into the southeastern Indian Ocean and western Pacific Ocean, causing the reduction of ITF transport over a deep layer. In contrast, the anomalous surface buoyancy flux in the Indo-Pacific affects the ocean temperature and salinity in a shallow upper layer, resulting in ITF changes in forms of high baroclinic mode structure with negligible impacts on the net ITF transport. A vertical partitioning index is proposed to distinguish the remote forcing via the AMOC and regional forcing in the Indo-Pacific Ocean, which could be useful for monitoring, attributing, and predicting the changing ITF transport under global warming.

Published
2023

19. Low Cloud–SST Feedback over the Subtropical Northeast Pacific and the Remote Effect on ENSO Variability

Author

Liu Yang, Shang-Ping Xie, Samuel S. P. Shen, Jing-Wu Liu, and Yen-Ting Hwang

Subjects
Atmospheric Science
Abstract

Low clouds frequent the subtropical northeastern Pacific Ocean (NEP) and interact with the local sea surface temperature (SST) to form positive feedback. Wind fluctuations drive SST variability through wind–evaporation–SST (WES) feedback, and surface evaporation also acts to damp SST. This study investigates the relative contributions of these feedbacks to NEP SST variability. Over the summer NEP, the low cloud–SST feedback is so large that it exceeds the evaporative damping and amplifies summertime SST variations. The WES feedback causes the locally enhanced SST variability to propagate southwestward from the NEP low cloud deck, modulating El Niño–Southern Oscillation (ENSO) occurrence upon reaching the equator. As a result, a second-year El Niño tends to occur when there are significant warm SST anomalies over the subtropical NEP in summer following an antecedent El Niño event and a second-year La Niña tends to occur when there are significant cold SST anomalies over the subtropical NEP in summer following an antecedent La Niña event The mediating role of the NEP low cloud–SST feedback is confirmed in a cloud-locking experiment with the Community Earth System Model, version 1 (CESM1). When the cloud–ocean coupling is disabled, SST variability over the NEP weakens and the modulating effect on ENSO vanishes. The nonlocal effect of the NEP low cloud–SST feedback on ENSO has important implications for climate prediction.

Published
2023

20. Ocean currents show global intensification of weak tropical cyclones

Author

Guihua Wang, Lingwei Wu, Wei Mei, and Shang-Ping Xie

Subjects
Multidisciplinary
Abstract

Theorysup1/supand numerical modellingsup2/supsuggest that tropical cyclones (TCs) will strengthen with rising ocean temperatures. Even though models have reached broad agreement on projected TC intensificationsup3-5/sup, observed trends in TC intensity remain inconclusive and under active debatesup6-10/supin all ocean basins except the North Atlantic, where aircraft reconnaissance data greatly reduce uncertaintiessup11/sup. The conventional satellite-based estimates are not accurate enough to ascertain the trend in TC intensitysup6,11/sup, suffering from contamination by heavy rain, clouds, breaking waves and spraysup12/sup. Here we show that weak TCs (that is, tropical storms to category-1 TCs based on the Saffir-Simpson scale) have intensified in all ocean basins during the period 1991-2020, based on huge amounts of highly accurate ocean current data derived from surface drifters. These drifters have submerged 'holy sock' drogues at 15 m depth to reduce biases induced by processes at the air-sea interface and thereby accurately measure near-surface currents, even under the most destructive TCs. The ocean current speeds show a robust upward trend of ~4.0 cm ssup-1/supper decade globally, corresponding to a positive trend of 1.8 m ssup-1/supper decade in the TC intensity. Our analysis further indicates that globally TCs have strengthened across the entirety of the intensity distribution. These results serve as a historical baseline that is crucial for assessing model physics, simulations and projections given the failure of state-of-the-art climate models in fully replicating these trendssup13/sup.

Published
2022

21. Buoyancy Forcing Dominates the Cross-Equatorial Ocean Heat Transport Response to Northern Hemisphere Extratropical Cooling

Author

Matthew T. Luongo, Shang-Ping Xie, and Ian Eisenman

Subjects
Climate Action, Atmosphere-ocean interaction, Energy transport, Intertropical convergence zone, Atmospheric Science, Geomatic Engineering, Meridional overturning circulation, Meteorology & Atmospheric Sciences, Oceanography, Life Below Water, Atmospheric Sciences
Abstract

Cross-equatorial ocean heat transport (OHT) changes have been found to damp meridional shifts of the intertropical convergence zone (ITCZ) induced by hemispheric asymmetries in radiative forcing. Zonal-mean energy transport theories and idealized model simulations have suggested that these OHT changes occur primarily due to wind-driven changes in the Indo-Pacific’s shallow subtropical cells (STCs) and buoyancy-driven changes in the deep Atlantic meridional overturning circulation (AMOC). In this study we explore the partitioning between buoyancy and momentum forcing in the ocean’s response. We adjust the top-of-atmosphere solar forcing to cool the Northern Hemisphere (NH) extratropics in a novel set of comprehensive climate model simulations designed to isolate buoyancy-forced and momentum-forced changes. In this case of NH high-latitude forcing, we confirm that buoyancy-driven changes in the AMOC dominate in the Atlantic. However, in contrast with prior expectations, buoyancy-driven changes in the STCs are the primary driver of the heat transport changes in the Indo-Pacific. We find that buoyancy-forced Indo-Pacific STC changes transport nearly 4 times the amount of heat across the equator as the shallower wind-driven STC changes. This buoyancy-forced STC response arises from extratropical density perturbations that are amplified by the low cloud feedback and communicated to the tropics by the ventilated thermocline. While the ocean’s specific response is dependent on the forcing scheme, our results suggest that partitioning the ocean’s total response to energy perturbations into buoyancy and momentum forcing provides basin-specific insight into key aspects of how the ocean damps ITCZ migrations that previous zonal-mean frameworks omit.

Published
2022

22. Widespread irreversible changes in surface temperature and precipitation in response to CO2 forcing

Author

Soong-Ki Kim, Jongsoo Shin, Soon-Il An, Hyo-Jeong Kim, Nari Im, Shang-Ping Xie, Jong-Seong Kug, and Sang-Wook Yeh

Subjects
Environmental Science (miscellaneous), Social Sciences (miscellaneous)
Abstract

Some climate variables do not show the same response to declining atmospheric CO2 concentrations as before the preceding increase. A comprehensive understanding of this hysteresis effect and its regional patterns is, however, lacking. Here we use an Earth system model with an idealized CO2 removal scenario to show that surface temperature and precipitation exhibit globally widespread irreversible changes over a timespan of centuries. To explore the climate hysteresis and reversibility on a regional scale, we develop a quantification method that visualizes their spatial patterns. Our experiments project that 89% and 58% of the global area experiences irreversible changes in surface temperature and precipitation, respectively. Strong irreversible response of surface temperature is found in the Southern Ocean, Arctic and North Atlantic Ocean and of precipitation in the tropical Pacific, global monsoon regions and the Himalayas. These global hotspots of irreversible changes can indicate elevated risks of negative impacts on developing countries.

Published
2022

23. How Does Sea Surface Temperature Drive the Intertropical Convergence Zone in the Southern Indian Ocean?

Author

Honghai Zhang, Richard Seager, and Shang-Ping Xie

Subjects
Atmospheric Science
Abstract

The Indian Ocean has an intriguing intertropical convergence zone (ITCZ) south of the equator year-round, which remains largely unexplored. Here we investigate this Indian Ocean ITCZ and the mechanisms for its origin. With a weak semiannual cycle, this ITCZ peaks in January–February with the strongest rainfall and southernmost location and a northeast–southwest orientation from the Maritime Continent to Madagascar, reaches a minimum around May with a zonal orientation, grows until its secondary maximum around September with a northwest–southeast orientation, weakens slightly until December, and then regains its mature phase in January. During austral summer, the Indian Ocean ITCZ exists over maximum surface moist static energy (MSE), consistent with convective quasi-equilibrium theory. This relationship breaks up during boreal summer when the surface MSE maximizes in the northern monsoon region. The position and orientation of the Indian Ocean ITCZ can be simulated well in both a linear dynamical model and the state-of-the-art Community Atmosphere Model version 6 (CAM6) when driven by observed sea surface temperature (SST). To quantify the contributions of the planetary boundary layer (PBL) and free-atmosphere processes to this ITCZ, we homogenize the free-atmosphere diabatic heating over the Indian Ocean in CAM6. In response, the ITCZ weakens significantly, owing to a weakened circulation and deep convection. Therefore, in CAM6, the SST drives the Indian Ocean ITCZ directly through PBL processes and indirectly via free-atmosphere diabatic heating. Their contributions are comparable during most seasons, except during the austral summer when the free-atmosphere diabatic heating dominates the mature-phase ITCZ. Significance Statement The intertropical convergence zone (ITCZ) is the globe-encircling band where trade winds converge and strong rainfall occurs in the tropics. Its rains provide life-supporting water to billions of people. Its associated latent heating invigorates the tropical atmospheric circulation and influences climate and weather across the planet. The ITCZ is located north of the equator in most tropical oceans, except in the Indian Ocean where it sits south of the equator year-around. In contrast to the well-known northern ITCZs, the origin of the southern ITCZ in the Indian Ocean remains unknown. This work provides the first explanation for how ocean surface temperature works together with processes in the lower and upper atmosphere to shape the unique ITCZ in the Indian Ocean.

Published
2022

24. Varying contributions of fast and slow responses cause asymmetric tropical rainfall change between CO2 ramp-up and ramp-down

Author

Shijie Zhou, Ping Huang, Shang-Ping Xie, Huang Gang, and Lin Wang

Subjects
Multidisciplinary
Abstract

Tropical rainfall is important for regional climate around the globe. In a warming climate forced by rising CO2, the tropical rainfall will increase over the equatorial Pacific where sea surface warming is locally enhanced. Here, we analyze an idealized CO2 removal experiment from the Carbon Dioxide Removal Model Intercomparison Project and show that the tropical rainfall change features a stronger pattern during CO2 ramp-down than ramp-up, even under the same global mean temperature increase, such as the 2°C goal of the Paris Agreement. The tropical rainfall during CO2 ramp-down increases over the equatorial Pacific with a southward extension, and decreases over the Pacific intertropical convergence zone and South Pacific convergence zone. The asymmetric rainfall changes between CO2 ramp-down and ramp-up result from time-varying contributions of the fast and slow oceanic responses to CO2 forcing, defined as the responses to abrupt CO2 forcing in the first 10 years and thereafter, respectively, in the abrupt-4xCO2 experiment. The fast response follows the CO2 evolution, but the slow response does not peak until 60 years after the CO2 peak. The slow response features a stronger El Niño-like pattern, as the ocean dynamical thermostat effect is suppressed under stronger subsurface warming. The delayed and stronger slow response leads to stronger tropical rainfall changes during CO2 ramp-down. Our results indicate that returning the global mean temperature increase to below a certain goal, such as 2°C, by removing CO2, may fail to restore tropical convection distribution, with potentially devastating effects on climate worldwide., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2022

25. Seasonal buildup and downward transfer of Warm Pool heat content by wind-driven ocean mixing

Author

Noel Gutierrez Brizuela, Yi Xia, Shang-Ping Xie, Matthew Alford, and James Moum

Abstract

Ocean heat stored in the Western Pacific Warm Pool (WPWP) helps drive some of the foremost modes of weather and climate variability including ENSO, Intraseasonal Oscillations, and tropical cyclones. To understand the associated coupled mechanisms that regulate ocean temperature, we use reanalysis and a novel moored microstructure dataset yielding estimates of the turbulent ocean heat flux (Jq(z)) to describe how WPWP mixing is regulated by seasonal, intraseasonal, and synoptic-scale atmospheric disturbances. It is argued that observed variations in Jq(z) impact seasonal-to-synoptic trends in SST and mixed-layer depth. Jq(z) is weakest during Spring (dry season), when heat fluxes into the ocean (Qnet > 0) create a shallow mixed layer (ML) of warm water that lays undisturbed atop the seasonal thermocline. In the Summer, westerly winds associated with the Asian Monsoon create favorable conditions for tropical depression-like (TD-like) storms, which in turn cause episodic spikes in Jq(z) that gradually deepen the ML and momentarily cool sea surface temperature (SST) while the background SST continues to rise. Towards the end of the summer, SST at our mooring was greater than 30.7 °C but rapidly dropped and stabilized below 29.5 °C after a strong pulse of the Madden-Julian Oscillation (MJO) cooled the upper ocean and deepened the ML for almost 15 days in a row. Enhanced upper ocean mixing continued to be episodic throughout the Fall as TD-like storms and intraseasonal disturbances moved over the mooring site. Mixing remained high throughout the Winter, when cold outbreaks forced the upper ocean at high frequencies and mean convective cooling (Qnet < 0) further contributed to mixing. A similar seasonality is observed at the thermocline level, where Jq(z) is enhanced by storm-driven near-inertial internal waves (NIWs) whose power peaks between Fall and Winter. While intraseasonal wind bursts had the greatest impact on near-surface mixing, synoptic disturbances generated greater-amplitude NIWs and thus had a greater potential to mix temperature gradients in the permanent thermocline. Lastly, we use reanalysis data to argue that storm-driven mixing shapes interannual relations between SST, storm activity, and the Asian Monsoon.

Published
2023

26. Irreversible changes in surface temperature and precipitation to CO2 forcing

Author

Soong-Ki Kim, Jongsoo Shin, Soon-Il An, Hyo-Jeong Kim, Nari Im, Shang-Ping Xie, Jong-Seong Kug, and Sang-Wook Yeh

Abstract

Anthropogenic global warming by carbon dioxide emissions may cause irreversible changes in a wide range of climate variables. A comprehensive understanding of this hysteresis effect and its regional patterns is, however, lacking. Here, we use the Community Earth System Model version 1.2 with a CO2 removal scenario to show that surface temperature and precipitation exhibit globally widespread irreversible changes. To explore the climate hysteresis and reversibility on a regional scale, we develop a novel method that quantifies their spatial patterns. Our experiments project that 89% and 58% of the global area experiences irreversible changes in surface temperature and precipitation, respectively. Strong irreversible response of surface temperature is found in the Arctic, Southern Ocean, and North Atlantic Ocean and of precipitation in the global monsoon regions, tropical Pacific, and the Himalayas. The identified global land hotspots of irreversible changes can indicate elevated risks of negative impacts on developing countries.

Published
2023

27. Observed subdaily variations in air–sea turbulent heat fluxes under different marine atmospheric boundary layer stability conditions in the Gulf Steam

Author

Xiangzhou Song, Xuehan Xie, Yunwei Yan, and Shang-Ping Xie

Abstract

Based on data collected from 14 air–sea buoys in the Gulf Stream, this study presents an examination of how the hourly air–sea turbulent heat fluxes vary on subdaily timescales under persistent marine atmospheric boundary layer (MABL) stability conditions. The annual mean magnitudes of the subdaily variations in the latent heat (LH) and sensible heat (SH) at all stations are determined to be 40 and 15 Wm-2, respectively. Under near-neutral conditions, the hourly anomalies of the air–sea humidity and temperature differences are the major drivers of the subdaily variations in LH and SH, respectively, followed by nonlinear effects and wind anomalies. Wind anomalies play dominant roles in determining the subdaily variations in LH and SH when the MABL is stable. In contrast, the contributions of the hourly anomalies of the air–sea differences in humidity and temperature are secondary but also significant. For a convectively unstable MABL, the wind anomalies control the subdaily variations in LH, whereas the subdaily variations in SH are dominated by the air–sea temperature anomalies. Accordingly, the above mechanism also controls the subdaily magnitudes. Quantitative estimates of the above relations are given in this study. However, compared to the observations when using daily mean SST, the subdaily variations in the reanalysis are found to be underestimated on average by 17% and 5% for LH and SH, respectively. Resolving the subdaily variations contributes significantly to the mean LH/SH estimates. For near-neutral and unstable MABLs, the subdaily contributions are O(100) and O(20) Wm-2 for LH and SH, respectively, while they are O(10) Wm-2 for LH/SH under stable conditions.

Published
2023

29. Radiative impacts of Californian marine low clouds on North Pacific climate

Author

Ayumu Miyamoto, Hisashi Nakamura, Shang-Ping Xie, Takafumi Miyasaka, and Yu Kosaka

Abstract

The northeastern Pacific climate system is featured by an extensive low-cloud deck off California on the southeastern flank of the subtropical high that accompanies intense northeasterly trades and relatively low sea surface temperatures (SSTs). This study investigates climatic impacts of the low-cloud deck by turning low-cloud radiative forcing on and off only within the subtropical northeastern Pacific in a coupled atmosphere-ocean model. The low-cloud radiative forcing causes a local SST decrease of up to 3ºC on an annual average, with the response extending southwestward through the wind-evaporation-SST (WES) feedback. The SST decrease peaks in summer under the seasonally enhanced insolation and the seasonally shallow ocean mixed layer. The lowered SST suppresses deep-convective precipitation that would otherwise occur in the absence of the low-cloud deck. The resultant anomalous diabatic cooling induces a surface anticyclonic response in summer and autumn as a baroclinic Matsuno-Gill pattern. On its equatorward flank, the enhanced trade winds further cool SST as the WES feedback, leading to the southwest propagation of the coupled response. The enhanced trades accompany the intensified upper-tropospheric westerlies, strengthening the vertical wind shear that, together with the lowered SST, acts to shield Hawaii from powerful hurricanes. On the basin scale, the anticyclonic surface wind response accelerates the North Pacific subtropical ocean gyre to speed up the Kuroshio by as much as 30%. SST thereby increases along the Kuroshio and its extension, intensifying upward turbulent heat fluxes from the ocean to increase precipitation.

Published
2023

30. Retaining Short-term Variability Reduces Biases in Wind Stress Overriding Simulations

Author

Matthew T. Luongo, Noel Brizuela, Ian Eisenman, and Shang-Ping Xie

Abstract

Positive feedbacks in climate processes can obscure the initial drivers of climate phenomena. Some recent global climate model (GCM) studies partially circumvent this issue by controlling the wind stress felt by the surface ocean such that the atmosphere and ocean become mechanically decoupled. Most mechanical decoupling studies have chosen to override wind stress with an annual climatology. In this study we introduce an alternative method of interannually variable overriding which maintains higher frequency momentum forcing of the surface ocean. Using CESM1, we then compare the size of the residuals between these two methods of overriding with a freely evolving control integration. We find that the simple act of overriding with a climatology, as has been done in previous studies, creates sea surface temperature (SST) residuals throughout the global oceans on the order of $0.5-1^\circ$C. This is substantially larger than residuals from the interannually variable overriding case introduced here. We attribute the SST biases in the climatological overriding case to the lack of synoptic and subseasonal variability, which creates too shallow of a mixed layer throughout the global surface ocean. This shoaling of the mixed layer reduces the effective heat capacity of the surface ocean and prevents anomalous heat from mixing into the thermocline. These results have implications for the reevaluation of past studies which have used climatological wind stress overriding and for avoiding these biases in future wind stress overriding studies by using interannually varying wind stress fields.

Published
2023

32. Global Warming Pattern Formation: The Role of Ocean Heat Uptake

Author

Shineng Hu, Shang-Ping Xie, and Sarah M. Kang

Subjects
Atmospheric Science
Abstract

This study investigates the formation mechanism of the ocean surface warming pattern in response to a doubling CO2 with a focus on the role of ocean heat uptake (or ocean surface heat flux change, ΔQnet). We demonstrate that the transient patterns of surface warming and rainfall change simulated by the dynamic ocean–atmosphere coupled model (DOM) can be reproduced by the equilibrium solutions of the slab ocean–atmosphere coupled model (SOM) simulations when forced with the DOM ΔQnet distribution. The SOM is then used as a diagnostic inverse modeling tool to decompose the CO2-induced thermodynamic warming effect and the ΔQnet (ocean heat uptake)–induced cooling effect. As ΔQnet is largely positive (i.e., downward into the ocean) in the subpolar oceans and weakly negative at the equator, its cooling effect is strongly polar amplified and opposes the CO2 warming, reducing the net warming response especially over Antarctica. For the same reason, the ΔQnet-induced cooling effect contributes significantly to the equatorially enhanced warming in all three ocean basins, while the CO2 warming effect plays a role in the equatorial warming of the eastern Pacific. The spatially varying component of ΔQnet, although globally averaged to zero, can effectively rectify and lead to decreased global mean surface temperature of a comparable magnitude as the global mean ΔQnet effect under transient climate change. Our study highlights the importance of air–sea interaction in the surface warming pattern formation and the key role of ocean heat uptake pattern.

Published
2022

34. Indo-Pacific Warming Induced by a Weakening of the Atlantic Meridional Overturning Circulation

Author

Andrew F. Thompson, Shang-Min Long, Shang-Ping Xie, and Shantong Sun

Subjects
Atmospheric Science, Climatology, Indo-Pacific, Geology
Abstract

The reorganization of the Atlantic meridional overturning circulation (AMOC) is often associated with changes in Earth’s climate. These AMOC changes are communicated to the Indo-Pacific basins via wave processes and induce an overturning circulation anomaly that opposes the Atlantic changes on decadal to centennial time scales. We examine the role of this transient, interbasin overturning response, driven by an AMOC weakening, both in an ocean-only model with idealized geometry and in a coupled CO2 quadrupling experiment, in which the ocean warms on two distinct time scales: a fast decadal surface warming and a slow centennial subsurface warming. We show that the transient interbasin overturning produces a zonal heat redistribution between the Atlantic and Indo-Pacific basins. Following a weakened AMOC, an anomalous northward heat transport emerges in the Indo-Pacific, which substantially compensates for the Atlantic southward heat transport anomaly. This zonal heat redistribution manifests as a thermal interbasin seesaw between the high-latitude North Atlantic and the subsurface Indo-Pacific and helps to explain why Antarctic temperature records generally show more gradual changes than the Northern Hemisphere during the last glacial period. In the coupled CO2 quadrupling experiment, we find that the interbasin heat transport due to a weakened AMOC contributes substantially to the slow centennial subsurface warming in the Indo-Pacific, accounting for more than half of the heat content increase and sea level rise. Thus, our results suggest that the transient interbasin overturning circulation is a key component of the global ocean heat budget in a changing climate.

Published
2022

35. Probabilistic Predictions from Deterministic Atmospheric River Forecasts with Deep Learning

Author

Stefano Alessandrini, W. Chapman, Aneesh C. Subramanian, Sebastian Lerch, Luca Delle Monache, F. Martin Ralph, Shang-Ping Xie, and Negin Hayatbini

Subjects
Atmospheric Science, Meteorology, business.industry, Deep learning, Probabilistic logic, Environmental science, Artificial intelligence, Atmospheric river, business
Abstract

Deep-learning (DL) postprocessing methods are examined to obtain reliable and accurate probabilistic forecasts from single-member numerical weather predictions of integrated vapor transport (IVT). Using a 34-yr reforecast, based on the Center for Western Weather and Water Extremes West-WRF mesoscale model of North American West Coast IVT, the dynamically/statistically derived 0–120-h probabilistic forecasts for IVT under atmospheric river (AR) conditions are tested. These predictions are compared with the Global Ensemble Forecast System (GEFS) dynamic model and the GEFS calibrated with a neural network. In addition, the DL methods are tested against an established, but more rigid, statistical–dynamical ensemble method (the analog ensemble). The findings show, using continuous ranked probability skill score and Brier skill score as verification metrics, that the DL methods compete with or outperform the calibrated GEFS system at lead times from 0 to 48 h and again from 72 to 120 h for AR vapor transport events. In addition, the DL methods generate reliable and skillful probabilistic forecasts. The implications of varying the length of the training dataset are examined, and the results show that the DL methods learn relatively quickly and ∼10 years of hindcast data are required to compete with the GEFS ensemble.

Published
2022

38. Prolonged thermocline warming by near-inertial internal waves in the wakes of tropical cyclones

Author

Noel Gutierrez Brizuela, Matthew Alford, Shang-Ping Xie, Janet Sprintall, Gunnar Voet, Sally Warner, Kenneth Hughes, and James Moum

Abstract

Tropical cyclones (TCs) mix vertical temperature gradients in the upper ocean and generate powerful near-inertial internal waves (NIWs) that propagate down into the deep ocean. Globally, downward mixing of heat during TC passage causes warming in the seasonal thermocline and pumps 0.15-0.6 PW of heat into the unventilated ocean. The final distribution of excess heat contributed by TCs is needed to understand subsequent consequences for climate; however, it is not well constrained by current observations. Here we show that NIWs generated by TCs drive thermocline mixing weeks after TC passage and thus greatly deepen the extent of downward heat transfer induced by TCs. Microstructure measurements of the turbulent diffusivity (κ) and turbulent heat flux (Jq) in the Western Pacific before and after the passage of three TCs indicate that mean thermocline values of κ and Jq increased by factors of 2-7 and 2-4 (95% confidence level) respectively after TC passage. Excess mixing is shown to be associated with the vertical shear of NIWs, demonstrating that studies of TC-climate interactions ought to represent NIWs and their mixing to accurately capture TC effects on ocean stratification.

Published
2023

40. Observational data for 'Prolonged thermocline warming by near-inertial internal waves in the wake of tropical cyclones'

Author

Noel Gutierrez Brizuela, Matthew H. Alford, Shang-Ping Xie, Janet Sprintall, Gunnar Voet, Sally J. Warner, Kenneth Hughes, and James N. Moum

Subjects
tropical cyclones, oceanography, ocean mixing
Abstract

Shipboard measurements of temperature, stratification, and turbulence, as well as ocean velocities and their near-inertial components.&nbsp

Published
2023
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42. Investigation of preoperative physical activity level in kidney transplant recipients and its impact on early postoperative recovery: A retrospective cohort study

Author

Guo Li, Qi-fan Guo, Shang-ping Zhao, Miao-wei Wang, Xia Zhang, Ao Wang, Chen-fan Gui, Qi-ling Tan, and Qiang Gao

Subjects
Surgery
Abstract

ObjectiveTo retrospectively investigate the preoperative physical activity (PA) level in kidney transplant recipients (KTRs) and its impact on early postoperative recovery.MethodsA total of 113 patients who received kidney transplantation at West China Hospital of Sichuan University were enrolled in this retrospective cohort study. According to the PA level measured by the Chinese version of the International Physical Activity Questionnaire—Long Version, the patients were allocated into the low PA level group (Group L, n = 55) and medium to high PA level group (Group MH, n = 58). The kidney function recovery indicators, including estimated glomerular filtration rate (eGFR), postoperative complications, postoperative length of stay (LOS), and unscheduled readmission within three months of discharge, were evaluated and documented. A association analysis was applied to analyze and compare the association between indicators.ResultsThe median PA levels of the KTRs were 1701.0 MTEs * min/week. Regarding the postoperative recovery indicators, the KTRs spent a mean time of 19.63 h to achieve transfer out of bed after the operation (Group L: 19.67 h; Group MH: 19.53 h; P = 0.952) and reached a mean distance of 183.10 m as the best ambulatory training score within two days after the operation (Group L: 134.91 m; Group MH: 228.79 m; P ρ = 0.497, P P = 0.913, 0.335, and 0.524) or postoperative complications, including DGF (P = 0.436), infection (P = 0.479), postoperative LOS (P = 0.103), and unscheduled readmission (P = 0.698), was found.ConclusionsThe preoperative PA level of KTRs is lower than that of the general population. KTRs with moderate or high preoperative PA levels showed higher ambulatory function in the early postoperative period than those with low preoperative PA levels, but no between-group differences in other early recovery indicators were observed.

Published
2023

43. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author

Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, 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Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weischenfeldt, Joachim, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Mark H, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.

Published
2023
Full Text
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44. Disentangling the mechanisms of equatorial Pacific climate change

Author

Sarah M. Kang, Yechul Shin, Hanjun Kim, Shang-Ping Xie, and Shineng Hu

Subjects
Climate Action, Multidisciplinary, Life Below Water
Abstract

Most state-of-art models project a reduced equatorial Pacific east-west temperature gradient and a weakened Walker circulation under global warming. However, the causes of this robust projection remain elusive. Here, we devise a series of slab ocean model experiments to diagnostically decompose the global warming response into the contributions from the direct carbon dioxide (CO 2 ) forcing, sea ice changes, and regional ocean heat uptake. The CO 2 forcing dominates the Walker circulation slowdown through enhancing the tropical tropospheric stability. Antarctic sea ice changes and local ocean heat release are the dominant drivers for reduced zonal temperature gradient over the equatorial Pacific, while the Southern Ocean heat uptake opposes this change. Corroborating our model experiments, multimodel analysis shows that the models with greater Southern Ocean heat uptake exhibit less reduction in the temperature gradient and less weakening of the Walker circulation. Therefore, constraining the tropical Pacific projection requires a better insight into Southern Ocean processes.

Published
2023

45. Radiative impacts of marine low clouds off California on the North Pacific climate system

Author

Nakamura, Hisashi, Miyamoto, Ayumu, Xie, Shang-Ping, Miyasaka, Takafumi, and Kosaka, Yu

Abstract

The Northeastern Pacific climate system is featured by a large-scale low-cloud deck off California on the southeastern flank of a subtropical high, which accompanies intense northeasterly trade winds and relatively low sea-surface temperature (SST), especially in the warm season. The climatic impacts of the low cloud deck are investigated by turning low-cloud radiative forcing on and off only within the subtropical Northeastern Pacificin a coupled atmosphere-ocean model. The radiative forcing lowers SST locally by as much as 3ºC, and the low-cloud impacts on the North Pacific subtropical high are found to maximize in summer under the seasonally enhanced insolation. In combination with the seasonally shallow ocean mixed layer, the SST decrease by low clouds off California peaks in summer, suppressing deep convective precipitation that would otherwise occur in the absence of the low-cloud deck. The resultant anomalous diabatic cooling induces a surface anticyclonic response in summer and autumn as a baroclinic Matsuno-Gill pattern. The consequent enhancement of the trade winds on its equatorward flank leads to further SST lowering that extends southwestward through the wind-evaporation-SST feedback. The enhanced trade winds accompany intensified upper-tropospheric westerlies, strengthening the vertical wind shear that, together with lowered SST, acts to shield Hawaii from powerful hurricanes. On the basin scale, the surface anticyclonic wind response accelerates the North Pacific subtropical ocean gyre to speed up the Kuroshio by as much as 30%. Thus, SST increases along the Kuroshio and its extension, intensifying upward turbulent heat fluxes from the ocean with increased precipitation., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2023

46. Southern Ocean Control of 2°C Global Warming in Climate Models

Author

So‐Jung Shin, Sang‐Wook Yeh, Soon‐Il An, Noel Keenlyside, Shang‐Ping Xie, and Jae‐Heung Park

Subjects
Earth and Planetary Sciences (miscellaneous), General Environmental Science
Abstract

Global warming will soon reach the Paris Agreement targets of 1.5°C/2°C temperature increase above pre-industrial levels. Under a business-as-usual scenario, the time to reach these targets varies widely among climate models. Using Coupled Model Intercomparison Project Phase 5 and 6, we show that a 2°C global warming is determined by Southern Ocean (SO) state closely tied with a low-level cloud (LLC) amount feedback strength during reference (1861–1900) period; climate models with cold SO tend to accompany more low-level cloudiness and Antarctic sea ice concentration due to a strong LLC amount feedback. Consequently, initially cold SO models tend to simulate a fast global warming by absorbing more downward shortwave radiation compared to initially warm SO models because more LLC disappears due to a strong LLC amount feedback during the 2°C rise. Our results demonstrate that climate models that correctly simulate initial SO state can improve 2°C warming projections with reduced uncertainties. publishedVersion

Published
2023

47. Combined burden and functional impact tests for cancer driver discovery using DriverPower

Author

Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Gallinger, Steven, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Boutros, Paul C, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chalmers, Don, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Dhalla, Noreen, Dhani, Neesha C, Dhir, Rajiv, DiBiase, Anthony, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gao, Jianjiong, Gao, Shengjie, Garraway, Levi, Garred, Øystein, Garrison, Erik, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grimmond, Sean M, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Haider, Syed, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Han, Leng, Hanna, George B, Hansmann, Martin, Harismendy, Olivier, Harliwong, Ivon, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Hersey, Peter, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

Published
2023
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48. Integrative pathway enrichment analysis of multivariate omics data

Author

Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, 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Vijver, Marc J, and Veer, L van’t

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.

Published
2023
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49. Pathway and network analysis of more than 2500 whole cancer genomes

Author

Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kellis, Manolis, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pons, Tirso, Reyes-Salazar, Iker, Rheinbay, Esther, Rubio-Perez, Carlota, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.

Published
2023
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50. Divergent mutational processes distinguish hypoxic and normoxic tumours

Author

Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.

Published
2023
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