<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2019 Workiva-->
<!--r:dd3d45a7-0da8-47bb-a3c3-61f8520e369a,g:f14ad036-b762-448e-8dce-df34663fa9a4-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/DocumentandEntityInformation" xlink:type="simple" xlink:href="dnli-20190930.xsd#DocumentandEntityInformation"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/DocumentandEntityInformation" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="dnli-20190930.xsd#CondensedConsolidatedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_def91bf7-b6d2-4508-9f4a-dc75fea5f762" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_8857d818-3df1-4569-a481-0b374aff4afb" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_def91bf7-b6d2-4508-9f4a-dc75fea5f762" xlink:to="loc_us-gaap_Liabilities_8857d818-3df1-4569-a481-0b374aff4afb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_80387f18-15b0-4010-b214-2043bea33e75" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_def91bf7-b6d2-4508-9f4a-dc75fea5f762" xlink:to="loc_us-gaap_CommitmentsAndContingencies_80387f18-15b0-4010-b214-2043bea33e75" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_aeec5df8-5c7b-4d4e-b933-697690c8625f" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_def91bf7-b6d2-4508-9f4a-dc75fea5f762" xlink:to="loc_us-gaap_StockholdersEquity_aeec5df8-5c7b-4d4e-b933-697690c8625f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_004b2b8f-68e9-42eb-901c-d5cf431f117b" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:to="loc_us-gaap_PreferredStockValue_004b2b8f-68e9-42eb-901c-d5cf431f117b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_5c644ab5-d358-4d9c-adf3-afdc08078a6b" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:to="loc_us-gaap_CommonStockValue_5c644ab5-d358-4d9c-adf3-afdc08078a6b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_2b1fa075-a545-4f1c-8b9b-4aa1a47c8f82" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:to="loc_us-gaap_AdditionalPaidInCapital_2b1fa075-a545-4f1c-8b9b-4aa1a47c8f82" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_99558d9b-9e23-4f00-9719-6399b5f1a776" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_99558d9b-9e23-4f00-9719-6399b5f1a776" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_891ce392-1392-4db0-9ac1-8b64d5e42cd0" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f1dc295a-7b9a-4b38-8314-567598fe3040" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_891ce392-1392-4db0-9ac1-8b64d5e42cd0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_8a0a5b4b-3e79-427d-bb83-03b69e742982" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:to="loc_us-gaap_LiabilitiesCurrent_8a0a5b4b-3e79-427d-bb83-03b69e742982" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_d99de11f-2e9f-44ae-92e4-17046264b852" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_d99de11f-2e9f-44ae-92e4-17046264b852" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_dd28d859-d2d8-4a04-992d-8209098737db" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_dd28d859-d2d8-4a04-992d-8209098737db" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_266abaf3-26ea-454a-9e69-4aeeb2d80845" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_266abaf3-26ea-454a-9e69-4aeeb2d80845" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredRentCreditNoncurrent_5af702e4-3c3f-405f-bf79-885030c42e06" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredRentCreditNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_5124b277-9277-4344-8a93-1e22818d5e32" xlink:to="loc_us-gaap_DeferredRentCreditNoncurrent_5af702e4-3c3f-405f-bf79-885030c42e06" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_f8dabb68-01f0-4316-be23-786e88163183" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_f8dabb68-01f0-4316-be23-786e88163183" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_267a9f60-e433-4eab-ac4d-cb5655945435" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:to="loc_us-gaap_AssetsCurrent_267a9f60-e433-4eab-ac4d-cb5655945435" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesNoncurrent_c76ab8f0-8f71-4217-b23c-623a3a0315e8" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MarketableSecuritiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:to="loc_us-gaap_MarketableSecuritiesNoncurrent_c76ab8f0-8f71-4217-b23c-623a3a0315e8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_e3f5a8d6-c998-4074-8e7c-b2e62214d394" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_e3f5a8d6-c998-4074-8e7c-b2e62214d394" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_fae4f5b0-6cc4-486d-81a8-d6978687fee0" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_b21ff141-df5b-40e1-8409-2ada829ff0f0" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_fae4f5b0-6cc4-486d-81a8-d6978687fee0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_203a5bb8-15a8-4256-b5bb-90fceecfd3e7" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_3f6f4753-8f4b-45fd-8136-fcbf4beac1d7" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_203a5bb8-15a8-4256-b5bb-90fceecfd3e7" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_3f6f4753-8f4b-45fd-8136-fcbf4beac1d7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesCurrent_90fe235c-15e7-4df4-8e13-249c338239b6" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MarketableSecuritiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_203a5bb8-15a8-4256-b5bb-90fceecfd3e7" xlink:to="loc_us-gaap_MarketableSecuritiesCurrent_90fe235c-15e7-4df4-8e13-249c338239b6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_367ec6e0-090a-4b51-b7d2-112514c269f1" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_203a5bb8-15a8-4256-b5bb-90fceecfd3e7" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_367ec6e0-090a-4b51-b7d2-112514c269f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_6f6a8bb4-a400-4da7-ba7d-5f84d3fe89d1" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:to="loc_us-gaap_AccountsPayableCurrent_6f6a8bb4-a400-4da7-ba7d-5f84d3fe89d1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_8a787509-0355-4b04-a6f8-b08c81d59c2b" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_8a787509-0355-4b04-a6f8-b08c81d59c2b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_84ff1870-3d2d-42e1-ad11-f961dd3325da" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_84ff1870-3d2d-42e1-ad11-f961dd3325da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_57518dda-bd07-4b81-b4fa-7d40b1372ada" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_57518dda-bd07-4b81-b4fa-7d40b1372ada" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesCurrent_819c10de-49d2-4e71-99e4-7f6c4da9a41a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherLiabilitiesCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_fd20dc5e-2fac-46fd-aa09-b4161afa739d" xlink:to="loc_us-gaap_OtherLiabilitiesCurrent_819c10de-49d2-4e71-99e4-7f6c4da9a41a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="dnli-20190930.xsd#CondensedConsolidatedBalanceSheetsParenthetical"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CondensedConsolidatedBalanceSheetsParenthetical" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLoss" xlink:type="simple" xlink:href="dnli-20190930.xsd#CondensedConsolidatedStatementsofOperationsandComprehensiveLoss"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_9c164d70-ab69-473d-b0f8-8096453d2f06" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_45249543-2912-49ed-8f06-da3acbf3563f" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_9c164d70-ab69-473d-b0f8-8096453d2f06" xlink:to="loc_us-gaap_NetIncomeLoss_45249543-2912-49ed-8f06-da3acbf3563f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax_f4741c6a-94ad-47cb-9772-39977f8ab385" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_9c164d70-ab69-473d-b0f8-8096453d2f06" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax_f4741c6a-94ad-47cb-9772-39977f8ab385" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_2d4bc9ba-9fb5-48b4-b35e-c3bd16d06b24" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_0f26087d-f385-4e89-99dd-eeb72457a65c" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_2d4bc9ba-9fb5-48b4-b35e-c3bd16d06b24" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_0f26087d-f385-4e89-99dd-eeb72457a65c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossAttributableToParent_a08ddce5-fa94-45a3-8c62-a52ac8f2965a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossAttributableToParent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_2d4bc9ba-9fb5-48b4-b35e-c3bd16d06b24" xlink:to="loc_us-gaap_IncomeLossAttributableToParent_a08ddce5-fa94-45a3-8c62-a52ac8f2965a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_eb9278e1-9750-457e-bcdd-72fab3ebd350" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_1d96468f-7eaf-43d6-aabe-d99bd76fcb4a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_eb9278e1-9750-457e-bcdd-72fab3ebd350" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_1d96468f-7eaf-43d6-aabe-d99bd76fcb4a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_19348d7e-db1f-4b25-9e0d-5cf37ad3c675" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_eb9278e1-9750-457e-bcdd-72fab3ebd350" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_19348d7e-db1f-4b25-9e0d-5cf37ad3c675" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossAttributableToParent_1aca2260-722e-40e8-8578-c271d7285596" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossAttributableToParent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_32d2d58e-58fb-4973-90d6-d9791f52e130" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossAttributableToParent_1aca2260-722e-40e8-8578-c271d7285596" xlink:to="loc_us-gaap_OperatingIncomeLoss_32d2d58e-58fb-4973-90d6-d9791f52e130" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_06fcfe9c-2237-4c6f-8400-b7e0c010ad17" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossAttributableToParent_1aca2260-722e-40e8-8578-c271d7285596" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_06fcfe9c-2237-4c6f-8400-b7e0c010ad17" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_bcfa1c16-7688-4b23-a834-e06c325fa2b9" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_f0028cae-bab1-4a17-8772-cd69d74df4d4" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_bcfa1c16-7688-4b23-a834-e06c325fa2b9" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_f0028cae-bab1-4a17-8772-cd69d74df4d4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_62dceac6-6f62-4bde-8b0e-d3f36ea94f78" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_bcfa1c16-7688-4b23-a834-e06c325fa2b9" xlink:to="loc_us-gaap_OperatingExpenses_62dceac6-6f62-4bde-8b0e-d3f36ea94f78" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="dnli-20190930.xsd#ConsolidatedStatementsofStockholdersEquity"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="dnli-20190930.xsd#ConsolidatedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/ConsolidatedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_930bb604-2c1c-47e3-8ac4-ebd8a15ccee2" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireMarketableSecurities_f9866243-7237-4d0f-9a0a-85ccd4c78ee8" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsToAcquireMarketableSecurities"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_930bb604-2c1c-47e3-8ac4-ebd8a15ccee2" xlink:to="loc_us-gaap_PaymentsToAcquireMarketableSecurities_f9866243-7237-4d0f-9a0a-85ccd4c78ee8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_4f75e7be-becf-4124-b82e-4bd5a840b745" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_930bb604-2c1c-47e3-8ac4-ebd8a15ccee2" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_4f75e7be-becf-4124-b82e-4bd5a840b745" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_47fb6413-9732-44fa-a0e7-5e4460ae4d09" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_930bb604-2c1c-47e3-8ac4-ebd8a15ccee2" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_47fb6413-9732-44fa-a0e7-5e4460ae4d09" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_f56eb995-5305-4f95-a0fe-a1daea611590" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_37434787-a6a9-4c22-ba94-1fd0e77cc190" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_f56eb995-5305-4f95-a0fe-a1daea611590" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_37434787-a6a9-4c22-ba94-1fd0e77cc190" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_a8adb32d-8cb5-4831-abd7-f84c6ec45c42" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_f56eb995-5305-4f95-a0fe-a1daea611590" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_a8adb32d-8cb5-4831-abd7-f84c6ec45c42" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_1122acd5-bbdf-41b5-9419-d4ce290d490d" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_f56eb995-5305-4f95-a0fe-a1daea611590" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_1122acd5-bbdf-41b5-9419-d4ce290d490d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ec25c04c-c356-4512-b739-3d56e0e933db" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_6c27fcc7-8b45-4210-9713-a623ea8abb73" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ec25c04c-c356-4512-b739-3d56e0e933db" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_6c27fcc7-8b45-4210-9713-a623ea8abb73" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_dnli_ProceedsFromIssuanceOfCommonStockInConnectionWithCollaborationAgreement_0c0bbb6f-0b9a-4bea-a8a9-e73fc403a8de" xlink:href="dnli-20190930.xsd#dnli_ProceedsFromIssuanceOfCommonStockInConnectionWithCollaborationAgreement"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ec25c04c-c356-4512-b739-3d56e0e933db" xlink:to="loc_dnli_ProceedsFromIssuanceOfCommonStockInConnectionWithCollaborationAgreement_0c0bbb6f-0b9a-4bea-a8a9-e73fc403a8de" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfStockIssuanceCosts_ebf68d89-3225-4ffb-b28c-7d5260d46ec4" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsOfStockIssuanceCosts"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_ec25c04c-c356-4512-b739-3d56e0e933db" xlink:to="loc_us-gaap_PaymentsOfStockIssuanceCosts_ebf68d89-3225-4ffb-b28c-7d5260d46ec4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_6e55a074-c613-4e91-b41b-32e706e12e16" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_NetIncomeLoss_6e55a074-c613-4e91-b41b-32e706e12e16" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_9e29cd10-d6e8-4d24-b5d5-d7b6c2a1fdb4" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_9e29cd10-d6e8-4d24-b5d5-d7b6c2a1fdb4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_725da2b9-830c-46ed-95c6-74b3a855efed" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_ShareBasedCompensation_725da2b9-830c-46ed-95c6-74b3a855efed" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium_e38ab69c-5f2b-4424-a4f6-2183940bdc05" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium_e38ab69c-5f2b-4424-a4f6-2183940bdc05" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnSaleOfPropertyPlantEquipment_6e875426-044e-47be-856f-f177d68ec1d7" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_GainLossOnSaleOfPropertyPlantEquipment"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_GainLossOnSaleOfPropertyPlantEquipment_6e875426-044e-47be-856f-f177d68ec1d7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_5fa24416-4425-443e-bfe4-04ba5acdeb34" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_5fa24416-4425-443e-bfe4-04ba5acdeb34" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_ebc2b260-3696-4757-a4af-fd46c42c2289" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_ebc2b260-3696-4757-a4af-fd46c42c2289" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_53202625-6a10-47e0-99b6-08220be7719c" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_53202625-6a10-47e0-99b6-08220be7719c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_dnli_IncreaseDecreaseInDeferredRent_6e72b210-f3fb-4c27-beed-5ca641f3eee5" xlink:href="dnli-20190930.xsd#dnli_IncreaseDecreaseInDeferredRent"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_dnli_IncreaseDecreaseInDeferredRent_6e72b210-f3fb-4c27-beed-5ca641f3eee5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_50b9082b-e3a3-4379-abc1-ffaaa2ddfbd7" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="10" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_50b9082b-e3a3-4379-abc1-ffaaa2ddfbd7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_dnli_IncreaseDecreaseInNonCashOperatingLeaseExpense_9d142a62-dca9-4947-be59-76952816f2bf" xlink:href="dnli-20190930.xsd#dnli_IncreaseDecreaseInNonCashOperatingLeaseExpense"/>
    <link:calculationArc order="11" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_dnli_IncreaseDecreaseInNonCashOperatingLeaseExpense_9d142a62-dca9-4947-be59-76952816f2bf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNoncashIncomeExpense_6755b073-e906-4946-963f-55583f8d8e14" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OtherNoncashIncomeExpense"/>
    <link:calculationArc order="12" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_28808db3-23de-4a60-b368-a94c86c93aed" xlink:to="loc_us-gaap_OtherNoncashIncomeExpense_6755b073-e906-4946-963f-55583f8d8e14" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPolicies" xlink:type="simple" xlink:href="dnli-20190930.xsd#SignificantAccountingPolicies"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/SignificantAccountingPolicies" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="dnli-20190930.xsd#SignificantAccountingPoliciesPolicies"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesPolicies" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#SignificantAccountingPoliciesNarrativeDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/SignificantAccountingPoliciesNarrativeDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="dnli-20190930.xsd#FairValueMeasurements"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/FairValueMeasurements" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#FairValueMeasurementsTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/FairValueMeasurementsTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#FairValueMeasurementsDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/FairValueMeasurementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_68868b49-b280-49e7-8d84-d5c46ba1b8d5" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_84f42804-00f0-4dd7-bacf-1c9615d8d5e7" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DerivativeLiabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosure_68868b49-b280-49e7-8d84-d5c46ba1b8d5" xlink:to="loc_us-gaap_DerivativeLiabilities_84f42804-00f0-4dd7-bacf-1c9615d8d5e7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_ef8ace3a-827f-41a4-9765-60da68c10a78" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_098f2c39-d6f4-4be4-a835-ec3a13984a48" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_ef8ace3a-827f-41a4-9765-60da68c10a78" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_098f2c39-d6f4-4be4-a835-ec3a13984a48" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_64ad435a-6443-4c8d-ab3f-606e11840b91" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_ef8ace3a-827f-41a4-9765-60da68c10a78" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_64ad435a-6443-4c8d-ab3f-606e11840b91" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_c3005c6b-6a21-410c-bc13-96d9a3f68f61" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DerivativeAssets"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_ef8ace3a-827f-41a4-9765-60da68c10a78" xlink:to="loc_us-gaap_DerivativeAssets_c3005c6b-6a21-410c-bc13-96d9a3f68f61" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecurities" xlink:type="simple" xlink:href="dnli-20190930.xsd#CashandMarketableSecurities"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CashandMarketableSecurities" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#CashandMarketableSecuritiesTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesScheduleofRestrictedCashandCashEquivalentsDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CashandMarketableSecuritiesScheduleofRestrictedCashandCashEquivalentsDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesScheduleofRestrictedCashandCashEquivalentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_674c3315-fc1d-41b0-b1ec-6851db149d92" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_fe42d1b2-2bc6-4db9-a977-1e9a4cda280b" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_674c3315-fc1d-41b0-b1ec-6851db149d92" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_fe42d1b2-2bc6-4db9-a977-1e9a4cda280b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_d8e70b6c-734f-4d98-9439-04a7d2cbe847" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_674c3315-fc1d-41b0-b1ec-6851db149d92" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_d8e70b6c-734f-4d98-9439-04a7d2cbe847" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_802cb672-2bfd-49a5-8bf9-8df940100f11" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_674c3315-fc1d-41b0-b1ec-6851db149d92" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_802cb672-2bfd-49a5-8bf9-8df940100f11" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesSummaryofAvailableforSaleSecuritiesDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CashandMarketableSecuritiesSummaryofAvailableforSaleSecuritiesDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesSummaryofAvailableforSaleSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_77d00b51-9cdc-4409-9288-28ad26e812bb" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_aad3da30-8df6-45d0-99c2-64d666a546e3" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_77d00b51-9cdc-4409-9288-28ad26e812bb" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_aad3da30-8df6-45d0-99c2-64d666a546e3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_5dea40a3-e3c2-42e4-92e0-e2675f9bbb2a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_77d00b51-9cdc-4409-9288-28ad26e812bb" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_5dea40a3-e3c2-42e4-92e0-e2675f9bbb2a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_2f4e6b0a-67ef-4f06-9e8d-5b59d53f7add" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_77d00b51-9cdc-4409-9288-28ad26e812bb" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_2f4e6b0a-67ef-4f06-9e8d-5b59d53f7add" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesNarrativeDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CashandMarketableSecuritiesNarrativeDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CashandMarketableSecuritiesNarrativeDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstruments" xlink:type="simple" xlink:href="dnli-20190930.xsd#DerivativeFinancialInstruments"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/DerivativeFinancialInstruments" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#DerivativeFinancialInstrumentsTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsSummaryofForwardForeignCurrencyExchangeContractsOutstandingDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#DerivativeFinancialInstrumentsSummaryofForwardForeignCurrencyExchangeContractsOutstandingDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/DerivativeFinancialInstrumentsSummaryofForwardForeignCurrencyExchangeContractsOutstandingDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/Acquisition" xlink:type="simple" xlink:href="dnli-20190930.xsd#Acquisition"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/Acquisition" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/AcquisitionDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#AcquisitionDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/AcquisitionDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreements" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreements"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreements" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsSanofiDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsSanofiPerformanceObligationDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsTakedaDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsTakedaDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsTakedaDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSummaryofCollaborationRevenueDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsSummaryofCollaborationRevenueDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsSummaryofCollaborationRevenueDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/LicenseAgreements" xlink:type="simple" xlink:href="dnli-20190930.xsd#LicenseAgreements"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/LicenseAgreements" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/LicenseAgreementsDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#LicenseAgreementsDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/LicenseAgreementsDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingencies" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingencies"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingencies" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingenciesTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesNarrativeDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingenciesNarrativeDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesNarrativeDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_c214f47f-1728-4c59-9e15-8a95bf767151" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_0dec41f9-0ddb-49b0-beaa-3becc3b8ee35" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_c214f47f-1728-4c59-9e15-8a95bf767151" xlink:to="loc_us-gaap_OperatingLeaseLiability_0dec41f9-0ddb-49b0-beaa-3becc3b8ee35" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_65fcf415-7c32-47c4-a973-76dd360057d8" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_c214f47f-1728-4c59-9e15-8a95bf767151" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_65fcf415-7c32-47c4-a973-76dd360057d8" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails_1" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails_1"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseCommitmentsDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_ae65561a-6a86-432e-8bc3-a32f71ca9103" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_ae65561a-6a86-432e-8bc3-a32f71ca9103" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo_6998b31f-ae97-4214-88a6-1e98f4f0d09c" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo_6998b31f-ae97-4214-88a6-1e98f4f0d09c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour_6eb1933f-0294-46d2-b2e1-dfe6c599fc0d" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour_6eb1933f-0294-46d2-b2e1-dfe6c599fc0d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree_d34ffa7c-cf03-4fe7-8b45-b7afabb75d4a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree_d34ffa7c-cf03-4fe7-8b45-b7afabb75d4a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive_11500b71-ef1f-4e24-9204-c66339fef071" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive_11500b71-ef1f-4e24-9204-c66339fef071" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive_e3fce07b-4b30-4e4e-b953-9bd31d94551c" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_01377f58-ca27-44be-b1f5-005d36b0cd2d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive_e3fce07b-4b30-4e4e-b953-9bd31d94551c" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseReceivablesDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseReceivablesDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CommitmentsandContingenciesSummaryofCompanysFutureMinimumLeaseReceivablesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceived"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedFiveYears_ab6f9567-8e66-4b39-b07d-2feb85e925cb" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedFiveYears"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedFiveYears_ab6f9567-8e66-4b39-b07d-2feb85e925cb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedThereafter_9ecdb69f-bfbf-4cff-afb5-09e548dd8749" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedThereafter"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedThereafter_9ecdb69f-bfbf-4cff-afb5-09e548dd8749" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedRemainderOfFiscalYear_dfc3b0ca-6a84-4fe8-a9df-5dd904fddfea" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedRemainderOfFiscalYear"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedRemainderOfFiscalYear_dfc3b0ca-6a84-4fe8-a9df-5dd904fddfea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedTwoYears_94ea7536-c088-427e-8a9d-48e4c6273719" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedTwoYears"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedTwoYears_94ea7536-c088-427e-8a9d-48e4c6273719" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedThreeYears_fb222af0-06b8-42d0-a313-d3d35eb0efa6" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedThreeYears"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedThreeYears_fb222af0-06b8-42d0-a313-d3d35eb0efa6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedFourYears_b05e8fa3-0ab2-4a59-8a8b-2cd95116742a" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceivedFourYears"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceived_75ee26ec-8dcc-492d-8f82-dca9864ccacd" xlink:to="loc_us-gaap_LessorOperatingLeasePaymentsToBeReceivedFourYears_b05e8fa3-0ab2-4a59-8a8b-2cd95116742a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwards" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwards"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwards" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsNarrativeDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsNarrativeDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsNarrativeDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockOptionActivityDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsSummaryofStockOptionActivityDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockOptionActivityDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofAssumptionsUsedforEstimatingtheFairValueofStockOptionsGrantedDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsSummaryofAssumptionsUsedforEstimatingtheFairValueofStockOptionsGrantedDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofAssumptionsUsedforEstimatingtheFairValueofStockOptionsGrantedDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofRestrictedStockActivityDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsSummaryofRestrictedStockActivityDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofRestrictedStockActivityDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#StockBasedAwardsSummaryofStockBasedCompensationExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/StockBasedAwardsSummaryofStockBasedCompensationExpenseDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/NetLossPerShare" xlink:type="simple" xlink:href="dnli-20190930.xsd#NetLossPerShare"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/NetLossPerShare" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/NetLossPerShareTables" xlink:type="simple" xlink:href="dnli-20190930.xsd#NetLossPerShareTables"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/NetLossPerShareTables" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/NetLossPerShareScheduleofDilutiveSecuritiesNotIncludedinDilutedPerShareCalculationsDetails" xlink:type="simple" xlink:href="dnli-20190930.xsd#NetLossPerShareScheduleofDilutiveSecuritiesNotIncludedinDilutedPerShareCalculationsDetails"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/NetLossPerShareScheduleofDilutiveSecuritiesNotIncludedinDilutedPerShareCalculationsDetails" xlink:type="extended"/>
  <link:roleRef roleURI="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetailsDefault" xlink:type="simple" xlink:href="dnli-20190930.xsd#CollaborationAgreementsSanofiPerformanceObligationDetailsDefault"/>
  <link:calculationLink xlink:role="http://www.denalitherapeutics.com/role/CollaborationAgreementsSanofiPerformanceObligationDetailsDefault" xlink:type="extended"/>
</link:linkbase>
